Tetrazolyl substituted imidazo 1,2-a!pyridinylalkyl compounds for treatment of neurotoxic injury

ABSTRACT

A class of imidazo 1,2-a!pyridinylalkyl compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a compound of this class alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula: ##STR1## wherein each of R 22 , R 23  and R 24  is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl; wherein each of Y m  and Y n  is a spacer group independently selected methylene and ethylene radicals which may be unsubstituted and from methylene radicals which may be substituted with a group selected from halo, hydroxy and oxo; wherein each of m and n is a number independently selected from zero to two, inclusive; wherein each X and T is one or more groups independently selected from hydrido, alkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl and alkanoyl; or a pharmaceutically-acceptable salt thereof.

RELATED APPLICATION

This is a continuation of U.S. application Ser. No. 07/973,481, filedNov. 9, 1992, abandoned which is a continuation-in-part of U.S.application Ser. No. 07/616,590, filed Nov. 26, 1990, abandoned, whichis a continuation-in-part of Ser. No. 07/445,228 filed Dec. 4, 1989,abandoned.

FIELD OF THE INVENTION

This invention is in the field of clinical neurology and relatesspecifically to a class of compounds, compositions and methods forneuro-protective purposes such as controlling chronic or acuteneurotoxic injury or brain damage resulting from neuro-degenerativediseases. For example, these compounds are particularly useful fortreating neurotoxic injury which follows periods of anoxia or ischemiaassociated with stroke, cardiac arrest or perinatal asphyxia. Thecompounds would also be useful as anticonvulsants and analgesics.

BACKGROUND OF THE INVENTION

Unlike other tissues which can survive extended periods of hypoxia,brain tissue is particularly sensitive to deprivation of oxygen orenergy. Permanent damage to neurons can occur during brief periods ofhypoxia, anoxia or ischemia. Neurotoxic injury is known to be caused oraccelerated by certain excitatory amino acids (EAA) found naturally inthe central nervous system (CNS). Glutamate (Glu) is an endogenous aminoacid which has been characterized as a fast excitatory transmitter inthe mammalian brain. Glutamate is also known as a powerful neurotoxincapable of killing CNS neurons under certain pathological conditionswhich accompany stroke and cardiac arrest. Normal glutamateconcentrations are maintained within brain tissue by energy-consumingtransport systems. Under low energy conditions which occur duringconditions of hypoglycemia, hypoxia or ischemia, cells can releaseglutamate. Under such low energy conditions the cell is not able to takeglutamate back into the cell. Initial glutamate release stimulatesfurther release of glutamate which results in an extracellular glutamateaccumulation and a cascade of neurotoxic injury.

It has been shown that the sensitivity of central neurons to hypoxia andischemia can be reduced by either blockage of synaptic transmission orby the specific antagonism of postsynaptic glutamate receptors see S. M.Rothman et al, Annals of Neurology, Vol. 19, No. 2 (1986)!. Glutamate ischaracterized as a broad spectrum agonist having activity at threeneuronal excitatory amino acid receptor sites. These receptor sites arenamed after the amino acids which selectively excite them, namely:Kainate (KA), N-methyl-D-aspartate (NMDA or NMA) and quisqualate (QUIS).Glutamate is believed to be a mixed agonist capable of binding to andexciting all three receptor types.

Neurons which have EAA receptors on their dendritic or somal surfacesundergo acute excitotoxic degeneration when these receptors areexcessively activated by glutamate. Thus, agents which selectively blockor antagonize the action of glutamate at the EAA synaptic receptors ofcentral neurons can prevent neurotoxic injury associated with anoxia,hypoxia or ischemia caused by stroke, cardiac arrest or perinatalasphyxia.

Aminophosphonic acids have been investigated as neurotransmitterblockers see M. N. Perkins et al, Neuroscience Lett., 23, 333 (1981);and J. Davies et al, Neuroscience Lett., 21, 77 (1981)!. In particular,compounds such as 2-amino-4-(2-phosphonomethyl-phenyl)butyric acid and2-(2-amino-2-carboxy)ethylphenylphosphonic acid have been synthesizedfor evaluation as antagonists in blocking the action of theneurotransmitter compounds L-glutamic acid and L-aspartic acid K. Matobaet al, "Structural Modification of Bioactive Compounds II. Syntheses ofAminophosphonic Acids", Chem. Pharm. Bull., 32, (10) 3918-3925 (1984)!.

U.S. Pat. No. 4,657,899 to Rzeszotarski et al described a class of w-2-(phosphonoalkylenyl)phenyl!2-aminoalkanoic acids characterized asbeing selective excitatory amino acid neurotransmitter receptorblockers. These compounds are mentioned for use as anticonvulsants,antiepileptics, analgesics and cognition enhancers. Typical compounds ofthe class include 3- 2-phosphonomethylphenyl!-2-aminopropanoic acid and3- 2-(2-phosphonoethyl)phenyl!-2-aminopropanoic acid.

An analogue of 2-amino-7-phosphonaheptanoic acid, namely3-(2-carboxypiperazin-4-yl)propyl-1phosphonic acid CPP!, has beenreported as a potent and selective NMDA antagonist in an evaluation ofCPP binding to rat brain hippocamal tissue D. E. Murphy et al, J.Pharmacol. Exp. Ther., 240 (3), 778-784 (1987)!.

Several classes of imidazopyridine compounds are known having variouspharmaceutical uses. For example, EP#120,589 published 3 Oct. 1984describes certain imidazo-(1,2-a)pyridinylheterocyclic compounds for useas cardiotonic and antiulcer agents. Schering EP#33,094 published 5 Aug.1981 describes 3,8-disubstituted-imidazo-(1,2-a)pyridine compounds foruse as antisecretory and cyto-protective agents. Synthelabo U.S. Pat.No. 4,650,796 published 19 Feb. 1986 describes2-phenyl-3-acylaminomethylimidazo pyridine compounds as anxiolytic,hypnotic and anticonvulsant agents. Synthelabo U.S. Pat. No. 4,501,745describes imidazo-(1,2-a)-pyridinealkanoic acid derivatives asanxiolytic, hynotic and anticonvulsant agents. Schering U.S. Pat. No.4,450,164 describes phosphonic acid derivatives of imidazo(1,2-a)pyridine compounds for use as treatment of gastrointestinal diseasessuch as ulcers.

Ciba-Geigy U.S. Pat. No. 4,746,653 describes phosphono-substituted2-carboxy-2,3-dihydro or perhydroindolyl derivatives for use as NMDAantagonists to treat cerebral ischemia.

DESCRIPTION OF THE INVENTION

Control of neuropathological processes and the neuro-degenerativeconsequences thereof in mammals is provided by treating a mammalsusceptible to neurotoxic injury with an anti-excitotoxic effectiveamount of a compound characterized in having activity as an antagonistat a major neuronal excitatory amino acid receptor site, such as theNMDA receptor site. Such antagonist compounds may be selected from aclass of imidazo 1,2a!pyridinealkyl compounds defined by Formula I:##STR2## wherein each of A and B is a moiety independently selected fromcarboxylic acid, tetrazole, phosphorus-containing acids,sulfur-containing acids, thio-phosphoruscontaining acids and the amide,ester and salt derivatives of said acids; wherein each A moiety and Bmoiety may be optionally independently substituted at any substitutableposition by one or more groups selected from alkyl, allyl, cycloalkyl,cycloalkylalkyl, aryl and aralkyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more of alkyl, cycloalkyl, cycloalkylalkyl, alkenyl,alkynyl, sulfinyl, sulfonyl, aryl, aralkyl and heteroaryl, any one ofwhich spacer groups may be substituted at any substitutable positionwith one or more groups selected from alkyl, cycloalkyl,cycloalkylalkyl, oxo, exomethylene, halo, haloalkyl, alkenyl,cycloalkenyl, alkynyl, alkoxycarbonyl, aryl, aralkyl, hydroxy,hydroxyalkyl, alkoxy, aryloxy, alkoxyalkyl, aralkoxy, aralkylthio,cyano, cyanoamino, nitro, alkanoyl, aroyl, mercapto, alkylthio,arylthio, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, arylsulfonyl,heteroaryl, heteroarylalkyl, and saturated or partially unsaturatedheterocylic and heterocyclicalkyl, and amino and amido radicals of theformula ##STR3## wherein each of R¹, R², R³, R⁴, R⁵ and R⁶ isindependently selected from hydrido, alkyl, cycloalkyl, hydroxyalkyl,cycloalkylalkyl, alkoxyalkyl, aralkyl and aryl; wherein R¹ and R² takentogether, R³ and R⁴ taken together and R⁵ and R⁶ taken together may forma heterocyclic group having five to seven ring members including thenitrogen atom of said amino or amido radical and which heterocyclicgroup may further contain one or more hetero atoms as ring membersselected from oxygen, nitrogen and sulfur and which heterocyclic groupmay be saturated or partially unsaturated; wherein R¹ and R² takentogether and R³ and R⁴ taken together may form an aromatic heterocyclicgroup having five ring members including the nitrogen atom of said aminoor amido radical and which aromatic heterocyclic group may furthercontain one or more hetero atoms as ring atoms selected from oxygen,nitrogen and sulfur; wherein each of m and n is a number independentlyselected from zero to five, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, oxo, halo, haloalkyl,alkenyl, cycloalkenyl, alkynyl, aryl, aralkyl, hydroxy, hydroxyalkyl,alkoxy, aryloxy, alkoxyalkyl, alkoxycarbonyl, aralkoxy, aralkylthio,cyano, cyanoamino, nitro, alkanoyl, mercapto, alkylthio, arylthio,alkylsulfinyl, arylsulfinyl, alkylsulfonyl, arylsulfonyl, heteroaryl,heteroarylalkyl, and saturated or partially unsaturated heterocylic andheterocyclicalkyl, and amino and amido radicals of the formula ##STR4##wherein each of R¹, R², R³, R⁴, R⁵ and R⁶ is independently selected fromhydrido, alkyl, cycloalkyl, hydroxyalkyl, cycloalkylalkyl, alkoxyalkyl,aralkyl and aryl, and wherein R¹ and R² taken together, R³ and R⁴ takentogether and R⁵ and R⁶ taken together may form a heterocyclic grouphaving five to seven ring members including the nitrogen atom of saidamino or amido radical and which heterocyclic group may further containone or more hetero atoms as ring members selected from oxygen, nitrogenand sulfur and which heterocyclic group may be saturated or partiallyunsaturated; wherein R¹ and R² taken together and R³ and R⁴ takentogether may form an aromatic heterocyclic group having five ringmembers including the nitrogen atom of said amino or amido radical andwhich aromatic heterocyclic group may further contain one or more heteroatoms as ring atoms selected from oxygen, nitrogen and sulfur; or apharmaceutically-acceptable salt thereof.

A preferred class consists of compounds within Formula I wherein each ofA and B is a moiety independently selected from ##STR5## wherein each Wis independently selected from oxygen atom and sulfur atom; wherein eachof R⁷ through R²³ is independently selected from hydrido, alkyl, allyl,cycloalkyl, cycloalkylalkyl, aryl and aralkyl, with the proviso thateach of R⁸, R⁹, R¹¹ and R¹³ cannot be hydrido; wherein each of R⁷, R⁸and R⁹ is further independently selected from OR²⁴ wherein R²⁴ isselected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aryl andaralkyl; wherein each of R⁷, R⁸, R⁹, R¹¹, R¹³, R¹⁹ and R²¹ is furtherindependently selected from amino radical of the formula ##STR6##wherein each of R²⁵ and R²⁶ is independently selected from hydrido,alkyl, cycloalkyl, hydroxyalkyl, haloalkyl, cycloalkylalkyl,alkoxyalkyl, aralkyl and aryl, and wherein R²⁵ and R²⁶ taken togethermay form a heterocyclic group having five to seven ring membersincluding the nitrogen atom of said amino radical and which heterocyclicgroup may further contain one or more hetero atoms as ring membersselected from oxygen, nitrogen and sulfur and which heterocyclic groupmay be saturated or partially unsaturated; wherein R²⁵ and R²⁶ takentogether may form an aromatic heterocyclic group having five ringmembers including the nitrogen atom of said amino radical and whicharomatic heterocyclic group may further contain one or more hetero atomsas ring atoms selected from oxygen, nitrogen and sulfur; wherein each ofR¹⁹ and R²¹ may be further independently selected from hydroxy, alkoxy,alkylthio, aryloxy, arylthio, aralkylthio and aralkoxy;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more of alkyl, alkenyl, alkynyl, aryl and aralkyl, any oneof which spacer groups may be substituted at any substitutable positionwith one or more groups selected from alkyl, cycloalkyl,cycloalkylalkyl, oxo, halo, haloalkyl, alkenyl, cycloalkenyl, alkynyl,alkoxycarbonyl, aryl, aralkyl, hydroxy, hydroxyalkyl, alkoxy, aryloxy,alkoxyalkyl, aralkoxy, cyano, cyanoamino, nitro, alkanoyl, aroyl,mercapto, alkylthio, arylthio, alkylsulfinyl, alkyl- sulfonyl,arylsulfinyl, arylsulfonyl, and amino and amido radicals of the formula##STR7## wherein each of R¹, R², R³, R⁴, R⁵ and R⁶ is independentlyselected from hydrido, alkyl, cycloalkyl, hydroxyalkyl, cycloalkylalkyl,alkoxyalkyl, phenalkyl and phenyl and wherein R¹ and R² taken together,R³ and R⁴ taken together and R⁵ and R⁶ taken together may form aheterocyclic group having five to seven ring members including thenitrogen atom of said amino or amido radical and which heterocyclicgroup may further contain one or more hetero atoms as ring membersselected from oxygen, nitrogen and sulfur and which heterocyclic groupmay be saturated or a partially unsaturated; wherein R¹ and R² takentogether and R³ and R⁴ taken together may form an aromatic heterocyclicgroup having five ring members including the nitrogen atom of said aminoor amido radical and which aromatic heterocyclic group may furthercontain one or more hetero atoms as ring atoms selected from oxygen,nitrogen and sulfur; wherein each of m and n is a number independentlyselected from zero to four, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, halo, ha10alkyl, alkenyl,cycloalkenyl, alkynyl, aryl, aralkyl, hydroxy, hydroxyalkyl, alkoxy,aryloxy, alkoxyalkyl, aralkoxy, cyano, cyanoamino, nitro, alkanoyl,mercapto, alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl,arylsulfinyl, arylsulfonyl, and amino and amido radicals of the formula##STR8## wherein each of R¹, R², R³, R⁴, R⁵ and R⁶ is independentlyselected from hydrido, alkyl, cycloalkyl, hydroxyalkyl, cycloalkylalkyl,alkoxyalkyl, phenalkyl and phenyl and wherein R¹ and R² taken together,R³ and R⁴ taken together and R⁵ and R⁶ taken together may form aheterocyclic group having five to seven ring members including thenitrogen atom of said amino or amido radical and which heterocyclicgroup may further contain one or more hetero atoms as ring membersselected from oxygen, nitrogen and sulfur and which heterocyclic groupmay be saturated or partially unsaturated; wherein R¹ and R² takentogether and R³ and R⁴ taken together may form an aromatic heterocyclicgroup having five ring members including the nitrogen atom of said aminoor amido radical and which aromatic heterocyclic group may furthercontain one or more hetero atoms as ring atoms selected from oxygen,nitrogen and sulfur; or a pharmaceutically-acceptable acid addition saltthereof.

A more preferred class consists of compounds within Formula I whereineach of A and B is a moiety independently selected from ##STR9## whereineach w is independently selected from oxygen atom and sulfur atom;wherein each of R⁷ through R²³ is independently selected from hydrido,alkyl, allyl, cycloalkyl, cycloalkylalkyl, phenyl and phenalkyl, withthe proviso that each of R⁸, R⁹, R¹¹ and R¹³ cannot be hydrido; whereineach of R⁷, R⁸ and R⁹ is further independently selected from OR²⁴wherein R²⁴ is selected from hydrido, alkyl, cycloalkyl,cycloalkylalkyl, phenyl and phenalkyl; wherein each of R⁷, R⁸, R⁹, R¹¹,R¹³, R¹⁹ and R²¹ is further independently selected from amino radical ofthe formula ##STR10## wherein each of R²⁵ and R²⁶ is independentlyselected from hydrido, alkyl, cycloalkyl, hydroxyalkyl, haloalkyl,cycloalkylalkyl, alkoxyalkyl, aralkyl and aryl, and wherein R²⁵ and R²⁶taken together may form a heterocyclic group having five to seven ringmembers including the nitrogen atom of said amino radical and whichheterocyclic group may further contain one or more hetero atoms as ringmembers selected from oxygen, nitrogen and sulfur and which heterocyclicgroup may be saturated or partially unsaturated; wherein R²⁵ and R²⁶taken together may form an aromatic heterocyclic group having five ringmembers including the nitrogen atom of said amino radical and whicharomatic heterocyclic group may further contain one or more hetero atomsas ring atoms selected from oxygen, nitrogen and sulfur; wherein each ofR¹⁹ and R²¹ is further independently selected from hydroxy, alkoxy,phenoxy, benzyloxy, benzylthio, mercapto, alkylthio and phenylthio;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more of alkyl, alkenyl, alkynyl, aryl and aralkyl, any oneof which spacer groups may be substituted at any substitutable positionwith one or more groups selected from alkyl, cycloalkyl,cycloalkylalkyl, oxo, exomethylene, halo, haloalkyl, alkenyl,cycloalkenyl, alkynyl, phenyl, benzyl, hydroxyl hydroxyalkyl, alkoxy,phenoxy, alkoxyalkyl, benzyloxy, cyano, cyanoamino, nitro, alkanoyl,benzoyl, mercapto, alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl,arylsulfinyl, arylsulfonyl, and amino and amido radicals of the formula##STR11## wherein each of R¹, R², R³, R⁴, R⁵ and R⁶ is independentlyselected from hydrido, alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl,benzyl, phenyl, and wherein R¹ and R² taken together, R³ and R⁴ takentogether and R⁵ and R⁶ taken together may form a heterocyclic grouphaving five ring members including the nitrogen atom of said amino oramido radical and which heterocyclic group may further contain one ormore hetero atoms as ring members selected from oxygen, nitrogen andsulfur and which heterocyclic group may be saturated or partiallyunsaturated; wherein R¹ and R² taken together and R³ and R⁴ takentogether may form an aromatic heterocyclic group having five to sevenring members including the nitrogen atom of said amino or amido radicaland which aromatic heterocyclic group may further contain one or morehetero atoms as ring atoms selected from oxygen, nitrogen and sulfur;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, alkenyl,cycloalkenyl, alkynyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy,phenoxy, alkoxyalkyl, benzyloxy, cyano, cyanoamino, nitro, alkanoyl,mercapto, alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl,arylsulfinyl, arylsulfonyl, and amino and amido radicals of the formula##STR12## wherein each of R¹, R², R³, R⁴, R⁵ and R 6 is independentlyselected from hydrido, alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl,benzyl and phenyl; and wherein R¹ and R² taken together, R³ and R⁴ takentogether and R⁵ and R⁶ taken together may form a heterocyclic grouphaving five to seven ring members including the nitrogen atom of saidamino or amido radical and which heterocyclic group may further containone or more hereto atoms as ring members selected from oxygen, nitrogenand sulfur and which heterocyclic group may be saturated or partiallyunsaturated; wherein R¹ and R² taken together and R³ and R⁴ takentogether may form an aromatic heterocyclic group having five ringmembers including the nitrogen atom of said amino or amido radical andwhich aromatic heterocyclic group may further contain one or more heteroatoms as ring atoms selected from oxygen, nitrogen and sulfur; or apharmaceuticallyacceptable acid salt thereof.

An even more preferred class consists of compounds within Formula Iwherein each of A and B is a moiety independently selected from##STR13## each W is independently selected from oxygen atom and sulfuratom; wherein each of R⁷, R⁸, R²⁰, R²¹, R²², R²³ and R²⁴ isindependently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl,phenyl and benzyl, with the proviso that R⁸ cannot be hydrido; andwherein R²¹ is further selected from amino radicals of the formula##STR14## wherein each of R¹³ and R¹⁴ is independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenyl and benzyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more of alkyl, alkenyl, alkynyl, aryl and aralkyl, any oneof which spacer groups may be substituted at any substitutable positionwith one or more groups selected from alkyl, cycloalkyl, oxo,exomethylene, halo, haloalkyl, phenyl, benzyl, hydroxy, hydroxyalkyl,alkoxy, phenoxy, alkoxyalkyl, benzyloxy, cyano, alkanoyl, and amino andamido radicals of the formula ##STR15## wherein each of R¹, R², R³ andR⁴ is independently selected from hydrido, alkyl, phenyl and benzyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, alkenyl,cycloalkenyl, alkynyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy,alkoxyalkyl, benzyloxy, cyano, cyanoamino, alkanoyl, mercapto,alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl andarylsulfonyl, and amino and amido radicals of the formula ##STR16##wherein each of R¹, R², R³ and R⁴ is independently selected fromhydrido, alkyl, phenyl and benzyl; or a pharmaceutically-acceptable saltthereof.

A first sub-set of highly preferred compounds consists of those withinFormula I selected from compounds of Formula II ##STR17## wherein B isselected from ##STR18## wherein each of R²², R²³ and R²⁴ is selectedfrom hydrido, alkyl, allyl, cycloalkyl, cycloalkylalkyl, phenyl andbenzyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR19## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy, phenoxy,alkoxyalkyl, benzyloxy, cyano, alkanoyl, ##STR20## wherein each of R¹,R², R³ and R⁴ is independently selected from hydrido, alkyl and phenyl;wherein R²⁷ and R²⁸ may be taken together to form oxo or exomethylene;wherein each of R²⁹ and R³⁰ is independently selected from hydrido,alkyl, haloalkyl, phenyl, hydroxyalkyl and alkoxyalkyl; wherein each ofm and n is a number independently selected from zero to three,inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, alkenyl,cycloalkenyl, alkynyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy,phenoxy, alkoxyalkyl, benzyloxy, cyano, cyanoamino, alkanoyl, mercapto,alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl andarylsulfonyl, ##STR21## wherein each of R¹, R², R³ and R⁴ isindependently selected from hydrido, alkyl and phenyl; or apharmaceutically-acceptable salt thereof.

A more highly preferred class of compounds within the first sub-setdefined by Formula II consists of compounds of Formula III ##STR22##wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR23## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR24## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR25## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula III are thefollowing:

6-chloro-α,2-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;

α,2-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;

6-chloro-2-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine;

2-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;

2-(1H-tetrazol-5-yl)-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine;

α,2-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-methanol;

6-chloro-2-(1H-tetrazol-5-yl)-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine;

7-bromo-6-2-methoxy-2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 2-methoxy-2-(1H-tetrazol-5-yl) ethyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

7-bromo-6- 2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol -5-yl)imidazo1,2-a!pyridine;

7-bromo-6-2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

7-bromo-6-3-methoxy-3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

7-bromo-6- 3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 3-hydroxy-3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

5- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

7-bromo-6- 3-hydroxy-3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6-chloro-2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6-hydroxy-2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6-methoxy-2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

2,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

2,7-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

5-chloro-2,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6-chloro-3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6-hydroxy-3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6-methoxy-3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

3,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

3,7-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

5-chloro-3,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6-chloro-α,3-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;

α,3-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;

6-chloro-3-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine;

3-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;

3-(1H-tetrazol-5-yl)-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine;

3-(1H-tetrazol-5-yl)-6- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;

6-chloro-3-(1H-tetrazol-5-yl)-5- methoxy(1H-tetrazol-5yl)methyl!imidazo1,2-a!pyridine;

6-chloro-5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6-chloro-5- 2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

5- 2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

5- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6-chloro-5-2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

and the pharmaceutically-acceptible salts thereof.

Another more highly preferred class of compounds within the firstsub-set of compounds defined by Formula II consists of compounds ofFormula IV ##STR26## wherein each of R²² and R²³ is independentlyselected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl and cycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR27## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR28## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR29## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula IV are thefollowing:

6-chloro-5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6-chloro-5- (1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

5- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6- hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6-chloro-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

7-bromo-6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

7-bromo-6- 2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

7-bromo-6- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

7-bromo-6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

7-bromo-6- 3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6- 3-(1H-tetrazol-5-yl)propyl!imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6- 3-hydroxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

5- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

7-bromo-6- 3-hydroxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6-chloro-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-hydroxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6-methoxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

7-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

5-chloro-6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-chloro-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

6-hydroxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-methoxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

7-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-chloro-6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

6-chloro-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

5- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-chloro-5- (1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-chloro-5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine-3-carboxylic acid;

6-chloro-5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

6-chloro-5- 2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

5- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

6-chloro-5- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

and the pharmaceutically-acceptable salts thereof.

Another more highly preferred class of compounds within the firstsub-set defined by Formula II consists of compounds of Formula V##STR30## wherein R²⁴ is selected from hydrido, methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR31## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR32## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR33## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula V are thefollowing:

6-chloro-5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine-2-carboxylic acid;

5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-2-carboxylicacid;

6-chloro-5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-2-carboxylicacid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-2-carboxylic acid;

5- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-2-carboxylicacid;

6- hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-2-carboxylicacid;

6-chloro-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine-2-carboxylic acid;

7-bromo-6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-2-carboxylic acid;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-2-carboxylic acid;

7-bromo-6- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridine-2-carboxylicacid;

6- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridine-2-carboxylic acid;

6- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-2-carboxylic acid;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-2-carboxylic acid;

7-bromo-6- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-2-carboxylic acid;

7-bromo-6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridine-2-carboxylic acid;

6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridine-2-carboxylic acid;

7-bromo-6- 3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridine-2-carboxylic acid;

6- 3-(1H-tetrazol-5-yl)propyl!imidazo 1,2-a!pyridine-2-carboxylic acid;

6- 3-hydroxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridine-2-carboxylic acid;

5- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridine-2-carboxylic acid;

7-bromo-6- 3-hydroxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridine-2-carboxylic acid;

6-chloro-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

6-hydroxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

6-methoxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

7-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

5-chloro-6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

6-chloro-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

6-hydroxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

6-methoxy-5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

7-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

5-chloro-6-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

6-chloro-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine-3-carboxylic acid;

5- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-3-carboxylicacid;

6-chloro-5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-3-carboxylicacid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-3-carboxylic acid;

5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-3-carboxylicacid;

6- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-3-carboxylicacid;

6-chloro-5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine-3-carboxylic acid;

6-chloro-5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-3-carboxylic acid;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-3-carboxylic acid;

6-chloro-5- 2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-3-carboxylic acid;

5- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridine-3-carboxylic acid;

6- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-3-carboxylic acid;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-3-carboxylic acid;

6-chloro-5- 2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-3-carboxylic acid;

and the pharmaceutically-acceptable salts thereof.

A second sub-set of highly preferred compounds consists of thosecompounds within Formula I selected from compounds of Formula VI##STR34## wherein B is selected from ##STR35## wherein each of R²², R²³and R²⁴ is independently selected from hydrido, alkyl, cycloalkyl,cycloalkylalkyl, phenyl and benzyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR36## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy, phenoxy,alkoxyalkyl, benzyloxy, cyano, alkanoyl, ##STR37## wherein each of R¹,R², R³ and R⁴ is independently selected from hydrido, alkyl and phenyl;wherein R²⁷ and R²⁸ may be taken together to form oxo or exomethylene;wherein each of R²⁹ and R³⁰ is independently selected from hydrido,alkyl, haloalkyl, phenyl, hydroxyalkyl and alkoxyalkyl; wherein each ofm and n is a number independently selected from zero to three,inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, alkenyl,cycloalkenyl, alkynyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy,phenoxy, alkoxyalkyl, benzyloxy, cyano, cyanoamino, alkanoyl, mercapto,alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl andarylsulfonyl, ##STR38## wherein each of R¹, R², R³ and R⁴ isindependently selected from hydrido, alkyl and phenyl; or apharmaceutically-acceptable salt thereof.

A more highly preferred class of compounds within the second sub-setdefined by Formula VI consists of compounds of Formula VII ##STR39##wherein R²⁴ is selected from hydrido, methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR40## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR41## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR42## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula VII are thefollowing:

6-chloro-α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-aceticacid;

α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-acetic acid;

6-chloro-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-acetic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-acetic acid;

α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-acetic acid;

α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-acetic acid;

6-chloro-α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-aceticacid;

7-bromo-α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-6-propanoicacid;

α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoic acid;

7-bromo-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoic acid;

α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-propanoic acid;

7-bromo-α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoicacid;

7-bromo-α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoicacid;

α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoic acid;

7-bromo-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoic acid;

α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoic acid;

α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-butanoic acid;

7-bromo-α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoicacid;

6-chloro-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

6-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

6-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-carboxylic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-7-carboxylic acid;

5-chloro-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-carboxylic acid;

6-chloro-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

6-hydroxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

6-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-carboxylic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-7-carboxylic acid;

5-chloro-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-carboxylic acid;

6-chloro-α-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-aceticacid;

α-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-acetic acid;

6-chloro-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-acetic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-acetic acid;

α-hydroxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-acetic acid;

6-chloro-α-hydroxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-aceticacid;

6-chloro-α-methoxy-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine-5-propanoic acid;

α-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-propanoic acid;

6-chloro-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-propanoic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-propanoic acid;

α-hydroxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-propanoic acid;

α-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoic acid;

6-chloro-α-hydroxy-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine-5-propanoic acid;

and the pharmaceutically-acceptable salts thereof.

Another more highly preferred class of compounds within the secondsub-set defined by Formula VI consists of compounds of Formula VIII##STR43## wherein each of R²², R²³ and R²⁴ is independently selectedfrom hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyland cycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR44## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR45## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR46## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula VIII are thefollowing:

6-chloro-α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

6-chloro-2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-6-acetic acid;

6-chloro-α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

7-bromo-α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

7-bromo-2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

7-bromo-α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

7-bromo-α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

7-bromo-2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-5-butanoic acid;

7-bromo-α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

6-chloro-2-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

2-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

6-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

6-methoxy-2-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

2-phosphonoimidazo 1,2-a!pyridine-6-carboxylic acid;

2-phosphonoimidazo 1,2-a!pyridine-7-carboxylic acid;

5-chloro-2-phosphonoimidazo 1,2-a!pyridine-6-carboxylic acid;

6-chloro-3-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

3-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

6-hydroxy-3-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

6-methoxy-3-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

3-phosphonoimidazo 1,2-a!pyridine-6-carboxylic acid;

3-phosphonoimidazo 1,2-a!pyridine-7-carboxylic acid;

5-chloro-3-phosphonoimidazo 1,2-a!pyridine-6-carboxylic acid;

6-chloro-α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

6-chloro-3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-hydroxy-3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-6-acetic acid;

6-chloro-α-hydroxy-3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

6-chloro-α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

6-chloro-3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

α-hydroxy-3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

6-chloro-α-hydroxy-3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

and the pharmaceutically-acceptable salts thereof.

Another more highly preferred class of compounds within the secondsub-set defined by Formula VI consists of compounds of Formula IX##STR47## wherein each R²⁴ is independently selected from hydrido,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andcycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR48## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR49## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR50## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula IX are thefollowing:

6-chloro-α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

6-chloro-2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-6-acetic acid;

6-chloro-α-methoxy-2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

7-bromo-α-methoxy-2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

7-bromo-2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

7-bromo-α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

7-bromo-α-methoxy-2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

α-methoxy-2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

7-bromo-2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

α-methoxy-2-carboxyimidazo 1,2-a!pyridine-5-butanoic acid;

7-bromo-α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

6-chloroimidazo 1,2-a!pyridine-2,5-dicarboxylic acid;

imidazo 1,2-a!pyridine-2,5-dicarboxylic acid;

6-hydroxyimidazo 1,2-a!pyridine-2,5-dicarboxylic acid;

6-methoxyimidazo 1,2-a!pyridine-2,5-dicarboxylic acid;

imidazo 1,2-a!pyridine-2,6-dicarboxylic acid;

imidazo 1,2-a!pyridine-2,7-dicarboxylic acid;

5-chloroimidazo 1,2-a!pyridine-2, 6-dicarboxylic acid;

6-chloroimidazo 1,2-a!pyridine-3,5-dicarboxylic acid;

imidazo 1,2-a!pyridine-3,5-dicarboxylic acid;

6-hydroxyimidazo 1,2-a!pyridine-3,5-dicarboxylic acid;

6-methoxyimidazo 1,2-a!pyridine-3,5-dicarboxylic acid;

imidazo 1,2-a!pyridine-3,6-dicarboxylic acid;

imidazo 1,2-a!pyridine-3,7-dicarboxylic acid;

5-chloroimidazo 1,2-a!pyridine-3,6-dicarboxylic acid;

6-chloro-α-methoxy-3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

6-chloro-3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-hydroxy-3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-carboxyimidazo 1,2-a!pyridine-6-acetic acid;

6-chloro-α-hydroxy-3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

6-chloro-α-methoxy-3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

α-methoxy-3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

6-chloro-3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

α-hydroxy-3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

α-methoxy-3-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

6-chloro-α-hydroxy-3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

and the pharmaceutically-acceptable salts thereof.

A third sub-set of highly preferred compounds consists of thosecompounds within Formula I selected from compounds of Formula X##STR51## wherein B is selected from ##STR52## wherein each of R²², R²³and R²⁴ is independently selected from hydrido, alkyl, cycloalkyl,cycloalkylalkyl, phenyl and benzyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR53## wherein each of R²⁶ andR²⁷ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy, phenoxy,alkoxyalkyl, benzyloxy, cyano, alkanoyl, ##STR54## wherein each of R¹,R², R³ and R⁴ is independently selected from hydrido, alkyl and phenyl;wherein R²⁷ and R²⁸ may be taken together to form oxo or exomethylene;wherein each of R²⁹ and R³⁰ is independently selected from hydrido,alkyl, haloalkyl, phenyl, hydroxyalkyl and alkoxyalkyl; wherein each ofm and n is a number independently selected from zero to three,inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, alkenyl,cycloalkenyl, alkynyl, phenyl, benzyl, hydroxy, hydroxyalkyl, alkoxy,phenoxy, alkoxyalkyl, benzyloxy, cyano, cyanoamino, alkanoyl, mercapto,alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl andarylsulfonyl, ##STR55## wherein each of R¹, R², R³ and R⁴ isindependently selected from hydrido, alkyl and phenyl; or apharmaceutically-acceptable salt thereof.

A more preferred class of compounds within the third sub-set defined byFormula X consists of compounds of Formula XI ##STR56## wherein each ofR²² and R²³ is independently selected from hydrido, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR57## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR58## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive.

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR59## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula XI are thefollowing:

6-chloro-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!hydroxymethyl!phosphonic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!hydroxymethyl!phosphonicacid;

6-chloro-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!methyl!phosphonic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!methyl!phosphonic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!methoxymethyl!phosphonicacid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!hydroxymethyl!phosphonicacid;

6-chloro-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!methoxymethyl!phosphonic acid;

2- 7-bromo-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-methoxyethyl!!phosphonic acid;

2- 2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-methoxyethyl!!phosphonic acid;

2- 7-bromo-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!ethyl!!phosphonic acid;

2- 2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!ethyl!!phosphonicacid;

2- 2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-hydroxyethyl!!phosphonic acid;

2- 2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!-1-methoxyethyl!!phosphonic acid;

2- 7-bromo-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-hydroxyethyl!!phosphonic acid;

3- 7-bromo-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-methoxypropyl!!phosphonic acid;

3- 3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-methoxypropyl!!phosphonic acid;

3- 7-bromo -3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!propyl!!phosphonic acid;

3- 3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!propyl!!phosphonicacid;

3- -(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-hydroxypropyl!!phosphonic acid;

3- 3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!-1-methoxypropyl!!phosphonic acid;

3- 7-bromo-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-hydroxypropyl!!phosphonic acid;

6-chloro-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonic acid;

6-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonicacid;

6-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonicacid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!phosphonic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-7-yl!phosphonic acid;

5-chloro-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!phosphonic acid;

6-chloro-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonic acid;

6-hydroxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonicacid;

6-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonicacid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!phosphonic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-7-yl!phosphonic acid;

5-chloro-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!phosphonic acid;

6-chloro-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!methoxymethyl!phosphonic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!methoxymethyl!phosphonicacid;

6-chloro-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!methyl!phosphonic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!methyl!phosphonic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!hydroxymethyl!phosphonicacid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!methoxymethyl!phosphonicacid;

6-chloro-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!hydroxymethyl!phosphonic acid;

2- 6-chloro-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!-1-methoxyethyl!phosphonic acid;

2- 3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!-1-methoxyethyl!phosphonic acid;

2- 6-chloro-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!ethyl!phosphonic acid;

2- 3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!ethyl!phosphonic acid;

2- 3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!-1-hydroxyethyl!phosphonic acid;

2- 3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-methoxyethyl!phosphonic acid;

2- 6-chloro-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!-1-hydroxyethyl!phosphonic acid;

and the pharmaceutically-acceptable salts thereof.

Another more preferred class of compounds within the third sub-setdefined by Formula X consists of compounds of Formula XII ##STR60##wherein each of R²² and R²³ is independently selected from hydrido,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andcycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more groups of the formula ##STR61## wherein each of R²⁷ andR²⁸ is independently selected from hydrido, alkyl, cycloalkyl, halo,haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkanoyl,##STR62## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl;wherein each of m and n is a number independently selected from zero tothree, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, phenyl, benzyl, hydroxy,hydroxyalkyl, alkoxy, phenoxy, alkoxyalkyl, benzyloxy, alkanoyl,##STR63## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido and alkyl; or a pharmaceutically-acceptable salt thereof.

Specific compounds of particular interest within Formula XII are thefollowing:

6-chloro-5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-chloro-5-(phosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

5-(phosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

5-(methoxyphosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-chloro-5-(methoxyphosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

7-bromo-6-(2-methoxy-2-phosphonoethyl)imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6-(2-methoxy-2-phosphonoethyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

7-bromo-6-(2-phosphonoethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-(2-phosphonoethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-(2-hydroxy-2-phosphonoethyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

5-(2-methoxy-2-phosphonoethyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

7-bromo-6-(2-hydroxy-2-phosphonoethyl)imidazo1,2-a!pyridin-2-yl!phosphonic acid;

7-bromo-6-(3-methoxy-3-phosphonopropyl)imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6-(3-methoxy-3-phosphonopropyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

7-bromo-6-(3-phosphonopropyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-(3-phosphonopropyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-(3-hydroxy-3-phosphonopropyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

5-(3-methoxy-3-phosphonopropyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

7-bromo-6-(3-hydroxy-3-phosphonopropyl)imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6-chloroimidazo 1,2-a!pyridin-2,5-diyl!bisphosphonic acid;

imidazo 1,2-a!pyridin-2,5-diyl!bisphosphonic acid;

6-hydroxyimidazo 1,2-a!pyridin-2,5-diyl!bisphosphonic acid;

6-methoxyimidazo 1,2-a!pyridin-2,5-diyl!bisphosphonic acid;

imidazo 1,2-a!pyridin-2, 6-diyl!bisphosphonic acid;

imidazo 1,2-a!pyridin-2,7-diyl!bisphosphonic acid;

5-chloroimidazo 1,2-a!pyridin-2,6-diyl!bisphosphonic acid;

6-chloroimidazo 1,2-a!pyridin-3,5-diyl!bisphosphonic acid;

imidazo 1,2-a!pyridin-3,5-diyl!bisphosphonic acid;

6-hydroxyimidazo 1,2-a!pyridin-3,5-diyl!bisphosphonic acid;

6-methoxyimidazo 1,2-a!pyridin-3,5-diyl!bisphosphonic acid;

imidazo 1,2-a!pyridin-3,6-diyl!bisphosphonic acid;

imidazo 1,2-a!pyridin-3,7-diyl!bisphosphonic acid;

5-chloroimidazo 1,2-a!pyridin-3,6-diyl!bisphosphonic acid;

6-chloro-5-(methoxyphosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

5-(methoxyphosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

6-chloro-5-(phosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-(phosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

6-(methoxyphosphonomethyl)imidazo 1,2-a!pyridin -3-yl!phosphonic acid;

6-chloro-5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-chloro-5-(2-methoxy-2-phosphonoethyl)imidazo1,2-a!pyridin-3-yl!phosphonic acid;

5-(2-methoxy-2-phosphonoethyl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-chloro-5-(2-phosphonoethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-(2-phosphonoethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-(2-hydroxy -2-phosphonoethyl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-(2-methoxy-2-phosphonoethyl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

6-chloro-5-(2-hydroxy-2-phosphonoethyl)imidazo1,2-a!pyridin-3-yl!phosphonic acid;

and the pharmaceutically-acceptable salts thereof.

Another more preferred class of compounds within the third sub-setdefined by Formula X consists of compounds of Formula XIII ##STR64##wherein each of R²², R²³ and R²⁴ is independently selected from hydrido,methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andcycloheptyl;

wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more methylene or ethylene radicals of the formula ##STR65##wherein each of R²⁷ and R²⁸ is independently selected from hydrido,alkyl, halo, haloalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl andalkanoyl; wherein R²⁷ and R²⁸ may be taken together to form oxo orexomethylene; wherein each of R²⁹ and R³⁰ is independently selected fromhydrido, alkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; wherein each ofm and n is a number independently selected from zero to two, inclusive;

wherein each X and T is one or more groups independently selected fromhydrido, alkyl, cycloalkyl, halo, haloalkyl, hydroxy, hydroxyalkyl,alkoxy, alkoxyalkyl, and alkanoyl; or a pharmaceutically-acceptable saltthereof.

Specific compounds of particular interest within Formula XIII are thefollowing:

ethyl 5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

5-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 6- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

6-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 7- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

7-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 8- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

8-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 6-chloro-5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

6-chloro-5-(phosphonomethyl)imidazo 1,2-a!pyridine2-carboxylic acid;

ethyl 7-chloro-5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

7-chloro-5-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 5- (diethoxyphosphinyl)methyl!-7-methoxyimidazo1,2-a!pyridine-2-carboxylate;

7-methoxy-5-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 8-(diethoxyphosphinyl)-5-methylimidazo1,2-a!pyridine-2-carboxylate;

5-methyl-8-phosphonoimidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 5-(diethoxyphosphinyl)imidazo 1,2-a!pyridine-2-carboxylate;

ethyl 5-diethoxyphosphinyl)imidazo 1,2-a!pyridine-2-carboxylate,monohydrochloride;

5-phosphonoimidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 5- (diethoxyphosphinyl)hydroxymethyl!imidazo 1,2-a!pyridine-2-carboxylate;

ethyl 5- (diethoxyphosphinyl)hydroxymethyl!imidazo1,2-a!pyridine-2-carboxylate;

5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridine-2 -carboxylic acid;

ethyl 5- 2-(diethoxyphosphinyl)-E-ethenyl!imidazo1,2-a!pyridine-2-carboxylate;

5-(2-phosphono-E-ethenyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

5-(2-phosphonoethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 8- (diethoxyphosphinyl)methyl!-3-methylimidazo1,2-a!pyridine-2-carboxylate;

ethyl 8- (diethoxyphosphinyl)methyl!-3-methylimidazo1,2-a!pyridine-2-carboxylate;

3-methyl-8-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-3-carboxylate;

5-(phosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

6-(phosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

8-(phosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 7- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-3-carboxylate;

7-(phosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 6-chloro-5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-3-carboxylate;

6-chloro-5-(phosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 5- (diethoxyphosphinyl)methyl!-7-methoxyimidazo1,2-a!pyridine-3-carboxylate;

7-methoxy-5-(phosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 7-chloro-5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-3-carboxylate;

7-chloro-5-(phosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 8-(diethoxyphosphinyl)-5-methylimidazo1,2-a!pyridine-3-carboxylate;

5-methyl-8-phosphonoimidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 5-(diethoxyphosphinyl)imidazo 1,2-a!pyridine-3-carboxylate;

5-phosphonoimidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 5- 2-(diethoxyphosphinyl)-E-ethenyl!imidazo1,2-a!pyridine-3-carboxylate;

5-(2-phosphono-E-ethenyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

5-(2-phosphonoethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

ethyl 5- (diethoxyphosphinyl)hydroxymethyl!imidazo1,2-a!pyridine-3-carboxylate;

5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

5-(fluorophosphonomethyl)imidazo 1,2-a!pyridine-3-carboxylic acid;

and the pharmaceutically-acceptable salts thereof.

Another class of specific compounds of particular interest withinFormula I consists of the following compounds: 5-hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-2-carboxylicacid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-2-carboxylic acid;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-2-carboxylic acid;

6- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridine-2-carboxylic acid;

6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridine-2-carboxylic acid;

6- 3-(1H-tetrazol-5-yl)propyl!imidazo 1,2-a!pyridine-2-carboxylic acid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-2-carboxylic acid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-3-carboxylic acid;

5- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-3-carboxylicacid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine-3-carboxylic acid;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridine-3-carboxylic acid;

5- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridine-3-carboxylic acid;

5- hydroxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!imidazo1,2-a!pyridin-2-yl!phosphonic acid;

6- 3-(1H-tetrazol-5-yl)propyl!imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

5-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5- methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!imidazo1,2-a!pyridin-3-yl!phosphonic acid;

5- 2-(1H-tetrazol-5-yl)ethyl!imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

α,2-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;

2-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;

6- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 2-(1H-tetrazol-5-yl)ethyl!2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

6- 3-methoxy-3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

6- 3-(1H-tetrazol-5-yl)propyl!2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

α,3-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;

3-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;

5- 2-methoxy-2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine;

5- 2-(1H-tetrazol-5-yl)ethyl!3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!hydroxymethyl!phosphonicacid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!methyl!phosphonic acid;

2- 2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-methoxyethyl!!phosphonic acid;

2- 2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!ethyl!!phosphonicacid;

3- 3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-6-yl!-1-methoxypropyl!!phosphonic acid;

3- 3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-6-yl!propyl!!phosphonicacid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!phosphonic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!methoxymethyl!phosphonicacid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!methyl!phosphonic acid;

2- 3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridin-5-yl!-1-methoxyethyl!phosphonic acid;

2- 3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridin-5-yl!ethyl!phosphonic acid;

5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

5-(phosphonomethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-(2-methoxy-2-phosphonoethyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6-(2-phosphonoethyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

6-(3-methoxy-3-phosphonopropyl)imidazo 1,2-a!pyridin-2-yl!phosphonicacid;

6-(3-phosphonopropyl)imidazo 1,2-a!pyridin-2-yl!phosphonic acid;

imidazo 1,2-a!pyridin-2,5-diyl!bisphosphonic acid;

imidazo 1,2-a!pyridin-3,5-diyl!bisphosphonic acid;

5-(methoxyphosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-(phosphonomethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

5-(2-methoxy-2-phosphonoethyl)imidazo 1,2-a!pyridin-3-yl!phosphonicacid;

5-(2-phosphonoethyl)imidazo 1,2-a!pyridin-3-yl!phosphonic acid;

α-hydroxy-2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-acetic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-phosphonic-5-acetic acid;

α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-butanoic acid;

2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-carboxylic acid;

α-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-acetic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-propanoic acid;

3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-propanoic acid;

α-hydroxy-2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

2-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

2-phosphonoimidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

2-phosphonoimidazo 1,2-a!pyridine-6-butanoic acid;

2-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

3-phosphonoimidazo 1,2-a!pyridine-5-carboxylic acid;

α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

3-phosphonoimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

3-phosphonoimidazo 1,2-a!pyridine-5-propanoic acid;

α-hydroxy-2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

2-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

2-carboxyimidazo 1,2-a!pyridine-6-propanoic acid;

α-methoxy-2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

2-carboxyimidazo 1,2-a!pyridine-6-butanoic acid;

imidazo 1,2-a!pyridine-2,5-dicarboxylic acid;

imidazo 1,2-a!pyridine-3,5-dicarboxylic acid;

α-methoxy-3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

3-carboxyimidazo 1,2-a!pyridine-5-acetic acid;

α-methoxy-3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

3-carboxyimidazo 1,2-a!pyridine-5-propanoic acid;

ethyl 5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

5-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

6-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 7- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

7-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

8-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 6-chloro-5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate;

6-chloro-5-(phosphonomethyl)imidazo 1,2-a!pyridine2-carboxylic acid;

5-methyl-8-phosphonoimdazo 1,2-a!pyridine-2-carboxylic acid;

5-phosphonoimidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 5- (diethoxyphosphinyl)hydroxymethyl!imidazo1,2-a!pyridine-2-carboxylate;

5-(hydroxyphosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

ethyl 8- (diethoxyphosphinyl)methyl!-3-methylimidazo1,2-a!pyridine-2-carboxylate;

3-methyl-8-(phosphonomethyl)imidazo 1,2-a!pyridine-2-carboxylic acid;

and the pharmaceutically-acceptable salts thereof.

The term "hydrido" denotes a single hydrogen atom (H). This hydridogroup may be attached, for example, to a carbon atom to form ahydrocarbyl group, or attached to an oxygen atom to form a hydroxylgroup; or, as another example, two hydrido groups may be attached to acarbon atom to form a --CH₂ -- group. Where the term "alkyl" is used,either alone or within other terms such as "haloalkyl", "aralkyl" and"hydroxyalkyl", the term "alkyl" embraces linear or branched radicalshaving one to about ten carbon atoms. Preferred alkyl radicals arelinear or branched "lower alkyl" radicals having one to about fivecarbon atoms. Specific examples of alkyl groups are methyl, ethyl,n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl,isopentyl and neopentyl. The term "cycloalkyl", embraces radicals havingthree to ten carbon atoms, such as cyclopropyl and cyclobutyl. The term"exomethylene" denotes a ═CH₂ group attached as a side chain to a carbonatom of a radical which may be selected from radicals embraced by --CR²⁷R²⁸ -- for selections of Y_(m) and Y_(n), herein. The term "haloalkyl"embraces radicals wherein any one or more of the carbon atoms issubstituted with one or more halo groups, preferably selected frombromo, chloro and fluoro. Specifically embraced by the term "haloalkyl"are monohaloalkyl, dihaloalkyl and polyhaloalkyl groups. A monohaloalkylgroup, for example, may have either a bromo, a chloro, or a fluoro atomwithin the group. Dihaloalkyl and polyhaloalkyl groups may besubstituted with two or more of the same halo groups, or may have acombination of different halo groups. A dihaloalkyl group, for example,may have two bromo atoms, such as a dibromomethyl group, or two chloroatoms, such as a dichloromethyl group, or one bromo atom and one chloroatom, such as bromochloromethyl group. Examples of a polyhaloalkyl aretrifluoromethyl, 2,2,2-trifluoroethyl, perfluoroethyl and2,2,3,3-tetrafluoropropyl groups. The term "aryl" embraces aromaticradicals such as phenyl, biphenyl and naphthyl. The term "aralkyl"embraces aryl-substituted alkyl radicals such as benzyl, diphenylmethyland triphenylmethyl. The terms "benzyl" and "phenylmethyl" areinterchangeable. The term "alkoxy" embraces linear or branchedoxy-containing radicals having an alkyl portion of one to about tencarbon atoms, such as methoxy, ethoxy, isopropoxy and butoxy. The term"alkylthio" embraces radicals containing a linear or branched alkylgroup of one to about ten carbon atoms attached to a divalent sulfuratom, such as a methythio group. The terms "aryloxy" and "arylthio"denote, respectively, aryl groups having an oxygen or sulfur atomthrough which the radical is attached to a nucleus, examples of whichare phenoxy and phenylthio. The terms "sulfinyl" and "sulfonyl", whetherused alone or linked to other terms, denote respectively, divalentradicals >SO and >SO₂. The term "acyl" whether used alone, or within aterm such as acyloxy, denotes a radical provided by the residueremaining after removal of hydroxy from an organic acid, examples ofsuch radical being acetyl and benzoyl. The term "alkenyl" embraceslinear or branched radicals having two to about twenty carbon atoms,preferably three to about ten carbon atoms, and containing at least onecarbon-carbon double bond, which carbon-carbon double bond may haveeither cis or trans geometry within the alkenyl moiety. The term"alkynyl" embraces linear or branched radicals having two to abouttwenty carbon atoms, preferably two to about ten carbon atoms, andcontaining at least one carbon-carbon triple bond. Typical alkenyl andalkynyl groups may have one unsaturated bond, such as an allyl group, ormay have a plurality of unsaturated bonds, with such plurality of bondseither adjacent, such as allene-type structures, or in conjugation, orseparated by several saturated carbons. The terms "cycloalkenyl" and"cycloalkynyl" embrace cyclic radicals having three to about ten ringcarbon atoms including, respectively, one or more double or triple bondsinvolving adjacent ring carbons. The terms "alkoxy" and "alkoxyalkyl"embrace linear or branched oxy-containing radicals each having alkylportions of one to about ten carbon atoms, such as methoxy group. The"alkoxy" or "alkoxyalkyl" radicals may be further substituted with oneor more halo atoms, such as fluoro, chloro or bromo, to providehaloalkoxy or haloalkoxyalkyl groups. The terms "heteroaryl", "aromaticheterocyclic group" and "fully unsaturated heterocyclic group" embracearomatic ring systems containing one to four hetero atoms selected fromoxygen, nitrogen and sulfur in a ring system having five or six ringmembers which may include the nitrogen atom of an amino or amidoradical(as mentioned in the foregoing description).

Examples of such "heteroaryl" groups are thienyl, furanyl, pyridinyl,thiazolyl, pyrimidyl, isoazolyl and the following structures: ##STR66##Examples of heterocyclic groups, which may be saturated or partiallyunsaturated and having five to seven ring members including the nitrogenatom of amino or amido radical (as mentioned in the foregoingdescription) are the following: ##STR67## Also embraced within theforegoing definitions are fused ring radicals, i.e., radicals having twoor more fused rings either or both of which may be saturated, partiallyunsaturated or fully unsaturated, examples of which are the following:##STR68## The terms "heteroaryl" and "saturated or partially unsaturatedheterocyclic" are also specified as possible selections for the X, T andY substituents of Formula I compounds of this invention. Examples ofsuch terms are as illustrated above for the hetero-containing groupswhich incorporate an amino or amido radical nitrogen atom within theheteroaryl or heterocyclic group. Where the terms "heteroaryl" and"saturated or partially unsaturated heterocyclic" are specified asselections for X, T and Y, it is understood that such terms areconstrued in light of the foregoing description and exemplifications,with the exception that any of the specified groups may be attached atthe X, Y and T positions any attachable position on the group, includingthe amino or amido radical nitrogen atom. Any of these groups may beattached at the X, T and Y positions through an alkyl group. Thus,"heteroarylalkyl" would be exemplified by imidazolemethyl.

Within this class of compounds of the invention are thepharmaceutically-acceptable salts of the compounds of Formula I,including acid addition salts and base addition salts. The term"pharmaceutically-acceptable salts" embraces"pharmacologically-acceptable salts" commonly used to form alkali metalsalts and to form addition salts of free acids or free bases. The natureof the salt is not critical, provided that it is pharmaceuticallyacceptable. Suitable pharmaceutically-acceptable acid addition salts ofcompounds of Formula I may be prepared from an inorganic acid or from anorganic acid. Examples of such inorganic acids are hydrochloric,hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid.Appropriate organic acids may be selected from aliphatic,cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic andsulfonic classes of organic acids, examples of which are formic, acetic,propionic, succinic, glycolic, gluconic, lactic, malic, tartaric,citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic,glutamic, benzoic, anthranilic, p-hydroxybenzoic, salicyclic,phenylacetic, mandelic, embonic (pamoic), methansulfonic,ethanesulfonic, 2-hydroxyethanesulfonic, pantothenic, benzenesulfonic,toluenesulfonic, sulfanilic, mesylic, cyclohexylaminosulfonic, stearic,algenic, β-hydroxybutyric, malonic, galactaric and galacturonic acid.Suitable pharmaceutically-acceptable base addition salts of compounds ofFormula I include metallic salts made from calcium, lithium, magnesium,potassium, sodium and zinc or organic salts made fromN,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine,ethylenediamine, meglumine (N-methylglucamine) and procaine. All ofthese salts may be prepared by conventional means from the correspondingcompound of Formula I by reacting, for example, the appropriate acid orbase with the compound of Formula I.

Compounds of general Formula I can possess one or more asymmetric carbonatoms and are thus capable of existing in the form of optical isomers aswell as in the form of racemic or nonracemic mixtures thereof. Theoptical isomers can be obtained by resolution of the racemic mixturesaccording to conventional processes, for example by formation ofdiastereoisomeric salts by treatment with an optically active acid orbase. Examples of appropriate acids are tartaric, diacetyltartaric,dibenzoyltartaric, ditoluoyltartaric and camphorsulfonic acid and thenseparation of the mixture of diastereoisomers by crystallizationfollowed by liberation of the optically active bases from these salts. Adifferent process for separation of optical isomers involves the use ofa chiral chromatography column optimally chosen to maximize theseparation of the enantiomers. Still another available method involvessynthesis of covalent diastereoisomeric molecules by reacting compoundsof Formula I with an optically pure acid in an activated form or anoptically pure isocyanate. The synthesized diastereoisomers can beseparated by conventional means such as chromatography, distillation,crystallization or sublimation, and then hydrolyzed to deliver theenantiomericaly pure compound. The optically active compounds of FormulaI can likewise be obtained by utilizing optically active startingmaterials. These isomers may be in the form of a free acid, a free base,an ester or a salt.

General Synthetic Procedures

Compounds embraced by Formula I may be prepared in accordance withSchemes I-IV which follow: ##STR69##

The amine of alkyl substituted 2-aminopyridines of Step (a) is protectedas its pivaloyl derivative by reacting these amines with a slight excessof trimethylacetyl chloride in the presence triethylamine. This reactionis carried out in a chlorocarbon solvent such as CHCl₃ and CH₂ Cl₂ attemperatures between 0° C. and room temperature (r.t.). This product inStep (b) is then brominated in the benzylic position in a chlorocarbonsolvent such as CCl₄ using an equivalent of N-bromo-succinimide (NBS)and a catalytic amount of 2,2'-azobisisobutyronitrile (AIBN). Thereaction is carrie dout under a reflector spot lamp at solvent reflux.The product of this reaction in Step (c) is refluxed with 5 to 25%aqueous sulfuric acid providing the hydroxylated 2-aminopyridines. Thematerial is subsequently, Step (d), cyclized with an equivalent ofeither ethyl bromopyruvate or a-chloroformylacetate at r.t. in solventssuch as ethylene glycol dimethylether (DME) or dioxane. The resultingintermediate is then refluxed in ethanol (EtOH) for several hourscompleting the cyclization. The benzylic hydroxyl function of theproduct imidazopyridine in Step (e) is converted to the chloride byreaction with a slight excess of thionylchloride (SOCl₂) at r.t. in achlorocarbon solvent. Treatment of this benzylic chloride compound, Step(f), with an excess of triethyl phosphite in refluxing methyl ethylketone (MEK) containing a catalytic amount of sodium iodide produces theimidazopyridine phosphinate ester. A six to twelve hour reflux of thistriester as indicated in Step (g) in from 2 to 6N hydrochloric acid(HCl) yields to imidazopyridine phosphonic carboxylic acid product.##STR70##

The amine of alkyl substituted 2-aminopyridines of Step (a) is protectedas its phthalic derivative by mixing these amines with an equivalent ofphthalic anhydride. This mixture is heated neat at temperatures between180° and 200° C. This product is then brominated, Step (b), in thebenzylic position in a chlorocarbon solvent such as CCl₄ using anequivalent of N-bromosuccinimide (NBS) and a catalytic amount of2,2'-azobisosobutyronitrile (AIBN). The reaction is carried out under areflector spot lamp at solvent reflux. Treatment of the benzylic bromidecompound, Step (c), with an excess of triethyl phosphite in refluxingmethyl ethyl ketone (MEK) containing a catalytic amount of potassiumiodide (KI) produces the phosphinate ester. The product of the precedingaction dissolved in a chlorocarbon solvent such as CH₂ Cl₂ or CHCl₃,Step (d), is stirred with at least 3 equivalents of hydrazinemonohydrate for several hours at ambient temperature. The product ofthis reaction is subsequently cyclized, Step (e), with an equivalent ofeither ethyl bromopyruvate or a-chloroformylacetate at r.t. in solventssuch as ethylene glycol dimethylether (DME) or dioxane. The initialintermediate is then refluxed in ethanol (EtOH) for several hourscompleting the cyclization. A six to twelve hour reflux of this triesteras indicated in Step (f) in from 2 to 6N hydrochloric acid (HCl) yieldsto imidazopyridine phosphonic-carboxylic acid product. ##STR71##

The alkyl halo-2-aminopyridine of Step (a) cyclized with an equivalentof either ethyl bromopyruvate or a-chloroformylacetate at ambienttemperature in solvents such as ethylene glycol dimethylether (DME) ordioxane. The resulting intermediate is then refluxed in ethanol (EtOH)for several hours completing the cyclization. This halo-imidazopyridineproduct is, in Step (b), treated with 3 equivalents of diethylphosphitedissolved in an aromatic hydrocarbon solvent such as benzene or toluene.To this solution is added a catalytic amount oftetrakis(triphenylphosphine) Palladium (O) and one equivalent oftriethylamine. The desired material is obtained following a 20 to 30hour reflux of the reaction mixture. As indicated in Step (c), a six totwelve hour reflux of the triester in from 2 to 6N hydrochloric acid(HCl)provides the imidazopyridine phosphonic-carboxylic acid product.##STR72##

A hydroxyalkyl 2-aminopyridine is cyclized as illustrated in Step (a)with an equivalent of either ethyl bromopyruvate ora-chloro-formylacetate at r.t. in solvents such as ethylene glycoldimethylether (DME) or dioxane. The resulting intermediate is thenrefluxed in ethanol (EtOH) for several hours completing the cyclization.Pyridinium chlorochromate oxidation this product, Step (b), in achlorocarbon solvent such as CH₂ Cl₂ CHCl₃ is accomplished by stirringthe mixture at room temperature for several hours. In Step (c), thealdehyde, dissolved in an aromatic hydrocarbon solvent such as benzeneor toluene, is reacted at 60° to 80° C. for several hours with diethylphosphite in the presence of N,N-diisopropylethyl amine under an inertatmosphere. As indicated in Step (d), a six to twelve hour reflux of thetriester in from 2 to 6N hydrochloric acid (HCl) provides theimidazo-pyridine phosphonic-carboxylic acid product. Alternatively, inStep (e), the imidazopyridine is oxidized with periodinane in achlorocarbon solvent such as CH₂ Cl₂ or CHCl₃ to the heterocyclicketone. Step (g) illustrates a six to twelve hour reflux of the triesterin from 2 to 6N HCl to generate the imidazo-pyridinephosphonic-carboxylic acid product. Alternatively, the benzylic alcoholeof Step (f) is treated with an equivalent of diethylaminosulphurtrifluoride (Dast) in a chlorocarbon solvent such as CH₂ Cl₂ or CHCl₃ atambient temperature under an inert atmosphere to yield the fluoroanalog. The compound is subsequently converted in Step (i) to the fluoroimidazo-pyridine phosphonic carboxylic acid product.

The following Examples 1-105 are detailed descriptions of the methods ofpreparation of compounds of Formula I. These detailed preparations fallwithin the scope of, and serve to exemplify, the above described GenericProcedures which form part of the invention. These Examples 1-105 arepresented for illustrative purposes only and are not intended as arestriction on the scope of the invention. All parts are by weightunless otherwise indicated. Most of the commercially-available startingmaterials were obtained from Aldrich Chemical Co., Milwaukee, Wis.

EXAMPLE 1 ##STR73## 2,2-dimethyl-N-(6-methyl-2-pyridinyl)propanamide

A 3-L flask equipped with a nitrogen (N₂) inlet, thermometer andaddition funnel was charged with dichloromethane (CH₂ Cl₂, 1400 mL) and2-amino-6-methylpyridine (130 g, 1.2 mol, Aldrich). After cooling thereaction to 0° C. in a wet ice/water bath, triethylamine (Et₃ N, 151.5g, 1.5 mol) was added. Trimethylacetyl chloride (159.15 g, 1.32 mol) wasdiluted with CH₂ Cl₂ (100 mL) and added dropwise to the reaction over1.5 h. The reaction was stirred for an additional 30 min at roomtemperature. The salts were filtered from the reaction and the filtratewas washed twice with H₂ O. Drying the filtrate with anhydrous magnesiumsulfate (MgSO₄) and stripping all solvent in vacuo left a yellowishcolored solid. Recrystallization from diethyl ether (Et2O)/hexanes (Hex)provided 167.3 g (73%) of pure product. The identity of this materialand that of subsequent examples were confirmed by NMR (300 MHZ),microanalysis, and infrared spectroscopy, unless otherwise noted.

EXAMPLE 2 ##STR74## N-6-(bromomethyl)-2-pyridinyl!-2,2-dimethylpropanamide

Carbon tetrachloride (CCl₄, 300 mL) and the product from Example 1 (50.6g, 0.26 mol) were placed in a 1-L flask equipped with a N₂ inlet Thesolution was stirred until all solid dissolved. N-bromosuccinimide (NBS,46.8 g, 0.26 mol) was then added to the reaction flask, followed by2,2'-azobisisobutyronitrile (AIBN, 0.02 g). The reaction was heated toreflux for 7 h with a 500 watt reflector spot lamp. After cooling thereaction to room temperature, it was filtered and all solvent wasremoved under reduced pressure. Flash chromatography (15/85 ethylacetate (EtOAc)/Hex) provided 24.89 g (37%) of title product.

EXAMPLE 3 ##STR75## 6-amino-2-pyridinemethanol

The product of Example 2 (24.89 g, 96 mmol) and 10% (v/v) H₂ SO₄ (100mL) were combined in a 250 mL flask. The reaction was heated to refluxfor 8 h and then cooled to room temperature. The reaction was made basicwith aq K₂ CO₃ and extracted with EtOAc. The extracts were dried(MgSO₄), decolorized with activated charcoal, and filtered. Removal ofall solvent in vacuo gave 8.49 g (71%) of the desired product.

EXAMPLE 4 ##STR76## Ethyl S-(hydroxymethyl)imidazo1,2-a!pyridine-2-carboxylate (HCl)

To a 100 mL flask under a N₂ atmosphere were added ethylene glycoldimethyl ether (DME, 120 mL) and the product of Example 3 (8.49 g, 68mmol). After stirring for 20 min, ethyl bromopyruvate (13.5 g, 69 mmol)was added and the reaction allowed to stir at room temperature for 16 h.The resulting precipitate was filtered and washed once with Et₂ O. Thesolid was then suspended in absolute ethanol (abs EtOH, 35 mL) andheated to reflux for 4 h. The resulting solution was cooled to roomtemperature and all solvent removed in vacuo. Aqueous K₂ CO₃ was addedto the residue, and the product was extracted with CH₂ Cl₂. The extractswere dried (MgSO₄), treated with activated charcoal, filtered, andstripped to leave 9.09 g (60%) of the title compound.

EXAMPLE 5 ##STR77## Ethyl 5-(chloromethyl)imidazo 1,2-a!pyridine-2-carboxylate

To a 250 mL flask containing chloroform (CHCl₃, 100 mL) was added theproduct from Example 4 (4.65 g, 21 mmol), followed by the slow additionof thionylchloride (SOCl₂, 2.97 g, 25 mmol). After stirring 3 h, thesolvent was removed in vacuo. Aqueous K₂ CO₃ was added to the residueand the product extracted with EtOAc. After the extracts were dried(MgSO₄), all solvent was removed under reduced pressure to give 4.9 g(97%) of pure product.

EXAMPLE 6 ##STR78## Ethyl 5- (diethoxyphosphinyl)methyl!imidazo1,2a!pyridine-2-carboxylate

In a 250 mL flask equipped with N₂ inlet, condensor, and stopper werecombined the product from Example 5 (4.9 g, 20 mmol) and methyl ethylketone (MEK, 100 mL). Sodium iodide (NaI, 3 g, 20 mmol) was added to thereaction, which was allowed to stir at room temperature for 30 min.Triethyl phosphite (3.66 g, 22 mmol) was added and the reaction washeated to reflux for 4.5 h. After cooling to room temperature, aq K₂ CO₃was added, and the product was extracted with EtOAc. The extracts weredried (MgSO₄), decolorized with activated charcoal, filtered andstripped of all solvent to give the crude yellow product. Flashchromatography (96/4 EtOAc/EtOH) provided 2.65 g (39%) of clean titleproduct.

Analysis Calcd. for C₁₅ H₂₁ N₂ O₅ P (MW=340.32) C, 52.94; H, 6.22; N,8.23. Found C, 52.82; H, 6.51; N, 8.05.

EXAMPLE 7 ##STR79## 5-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid (HCl)

A 50 mL flask was charged with the product from Example 6 (2.0 g, 6mmol) and 4N. HCl (25 mL). The reaction was heated to reflux for 12 h.After cooling to room temperature, the solvent was removed in vacuo.Trituration of the residue with Et₂ O, and filtration of the titleproduct yielded 1.0 g of product HCl salt after oven drying.

Analysis Calcd. for C₉ H₉ N₂ O₅ P+1.25 HCl+1.25 H₂ O (MW=324.25) C,33.34; H, 3.96; N, 8.64. Found C, 33.71; H, 3.78; N, 8.55.

EXAMPLE 8 ##STR80## Methyl 6-amino-3-pyridinecarboxylate

To a 25 mL flask under a N₂ atmosphere was added methanol (MeOH, 15 mL)and 6-aminonicotinic acid (1.0 g, 7.2 mmol). The resulting suspensionwas cooled to 0° C. in a wet ice/water bath. Thionylchloride (1.69 g,14.4 mmol) was then added dropwise and the solution allowed to warm toroom temperature over 16 h. Additional SOCl₂ (1.63 g, 13.7 mmol) wasadded and the reaction heated to reflux for 7 h. The reaction was cooledto room temperature and evaporation of all solvent produced the titleHCl salt.

EXAMPLE 9 ##STR81## 6-amino-3-pyridinemethanol

A 250 mL 3-neck flask equipped with an addition funnel, an argon (Ar)inlet and a stopper was flame dried and cooled to room temperature. Drytetrahydrofuran (THF, 30 mL) was added to the flask, followed by 1M.lithium aluminum hydride (LAH) in Et₂ O (16 mL). After cooling thesolution to 0° C. with a wet ice/water bath, the product from Example 8(0.92 g, 6 mmol) suspended in THF (100 mL) was added dropwise. Thereaction was allowed to warm to room temperature and stir for 3 h. Thereaction was quenched with H₂ O, the salts filtered off and the filtratestripped to give 0.591 g (99%) of title material.

EXAMPLE 10 ##STR82## Ethyl 6-(hydroxymethyl)imidazo1,2-a!pyridine-2-carboxylate

To a 100 mL flask under a N₂ atmosphere were added DME (35 mL) and theproduct from Example 9 (0.60 g, 4.8 mmol). After stirring for 20 min,ethyl bromopyruvate (1.03 g, 5.3 mmol) was added and the reaction wasallowed to stir at room temperature for 16 h. The resulting precipitatewas filtered and washed once with Et₂ O. The solid was suspended in absEtOH (35 mL) and heated to reflux for 2 h. The resulting solution wascooled to room temperature and all solvent removed in vacuo. Aqueous K₂CO₃ was added to the residue, and the product was extracted with CH₂Cl₂. The extracts were dried (MgSO₄) and stripped to leave 0.793 g (75%)of title product.

EXAMPLE 11 ##STR83## Ethyl 6-(chloromethyl)imidazo1,2-a!pyridine-2-carboxylate

By the method of Example 5, the product from Example 10 (2.52 g, 11.4mmol) dissolved in CHCl₃ (100 mL) was reacted with SOCl₂ (1.5 g, 12.6mmol). Final workup provided 2.66 g (98%) of title compound.

EXAMPLE 12 ##STR84## Ethyl 6- (diethoxyphosphinyl)methyl!imidazo 1,2a!pyridine-2-carboxylate

By the method of Example 6, the product from Example 11 (2.66 g, 11.1mmol) was treated with NaI (1.67 g, 11.1 mmol) and triethyl phosphite(2.03 g, 12.2 mmol). Workup produced 1.61 g (43%) of title compound.

EXAMPLE 13 ##STR85## 6-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid (HCl)

By the procedure of Example 7, the product from Example 12 (0.21 gcrude) was refluxed in 4N. HCl (16 mL) for 24 h. Workup produced 0.1 gof the title HCl salt.

Analysis Calcd. for C₉ H₉ N₂ O₅ P+1.1 HCl+0.5 H₂ O (MW=305.26) C, 35.41H, 3.67; N, 9.18. Found C, 35.39; H, 3.58 N, 9.360

EXAMPLE 14 ##STR86## 2-4-(bromomethyl)-2-pyridinyl!-1H-isoindole-1,3(2H)-dione

Following the procedure of Example 32, equimolar amounts of2-aminopicoline and phthalic anhydride were reacted to give2-(4-methyl-2-pyridinyl)1H-isoindole-1,3(2H)-dione. This product (1.0 g,4.2 mmol) was then reacted with NBS (0.747 g, 4.2 mmol) in CH₂ Cl₂ (50mL), using the procedure of Example 2, to give the title compound.

EXAMPLE 15 ##STR87## Diethyl2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-4-pyridinyl!methyl!phosphonate

The product from Example 14, triethyl phosphite (7.66 g, 46 mmol) and acatalytic amount of potassium iodide were placed in a flask containingMEK (500 mL) under a N₂ atmosphere. The reaction was heated to refluxfor 11 h. After cooling to room temperature, the solid was filtered fromthe reaction mixture, and the filtrate stripped in vacuo. Aqueous K₂ CO₃was added to the residue, and the product extracted with EtOAc. Theextract was dried (MgSO₄), filtered and stripped of all solvent in vacuoto produce the crude product which was purified by flash chromatography(97/3 CHCl₃ /EtOH).

EXAMPLE 16 ##STR88## Diethyl (2-amino-4-pyridinyl)methyl!phosphonate

The product from Example 15 (1.4 g, 3.7 mmol) was dissolved in CH₂ Cl₂(10 mL) and placed in a 25 mL flask. Hydrazine monohydrate (0.187 g, 3.7mmol) was added to the flask, and the reaction was allowed to stir atroom temperature for 2 h. Two additional equivalents of hydrazinemonohydrate were added to drive the reaction to completion. Filteringand solvent removal under reduced pressure gave 0.87 g of crude titlecompound which was used without further purification.

EXAMPLE 17 ##STR89## Ethyl 7- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate

The product from Example 16 (0.87 g, 3.56 mmol) was dissolved in DME (25mL) and placed in a 100 mL flask. Ethyl bromopyruvate (0.76 g, 3.92mmol) was added to the flask, and the reaction was allowed to stir undera N₂ atmosphere for 16 h. After solvent removal in vacuo, the residuewas taken up in abs EtOH (25 mL) and refluxed for 5 h. The reaction wascooled to room temperature and solvent was removed in vacuo. The residuewas dissolved in aqueous K₂ CO₃ and the product extracted with EtOAc.Purification via a chromatotron (97/2/1 CH₂ Cl₂ /EtOH/NH₄ OH) produced0.38 g (32%) of title compound.

Analysis Calcd. for C₁₅ H₂₁ N₂ O₅ P (MW=340.31) C, 52.94; H, 6.22; N,8.23 Found C, 52.65; H, 6.20; N, 8.05.

EXAMPLE 18 ##STR90## 7-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid (HCl)

Following the procedure of Example 7, the product from Example 17 (0.32g, 0.9 mmol) was dissolved in 4N. HCl (25 mL). Final purificationprovided the title compound as the HCl salt.

Analysis Calcd. for C₉ H₉ N₂ O₅ P+0.9 HCl+0.5 H₂ O (MW=297.97) C, 36.28;H, 3.69; N, 9.40. Found C, 36.31; H, 3.63; N, 9.18.

EXAMPLE 19 ##STR91## 2-amino-3-(hydroxymethyl)pyridine

This compound was synthesized referencing the method of Murakami,et.al., Bull. Chem. Soc.. Jap. 1973, 46(7), 2187.

EXAMPLE 20 ##STR92## Ethyl 8-(hydroxymethyl)imidazo1,2-a!pyridine-2-carboxylate

Following the procedure of Example 10, the product from Example 19 (5.0g, 40 mmol) was combined with ethyl bromopyruvate (8.58 g, 44 mmol) inDME (50 mL). Final product purification gave 5.24 g (60%) of titlecompound.

EXAMPLE 21 ##STR93## Ethyl 8-(chloromethyl)imidazo1,2-a!pyridine-2-carboxylate

The product from Example 20 (5.0 g, 23 mmol) was dissolved in CHCl₃ (50mL) and placed in a 100 mL flask. Thionylchloride (2.97 g, 25 mmol) wasadded dropwise to the reaction. The reaction was heated to reflux for 1h. After cooling the reaction to room temperature, aq KHCO₃ was added tothe solution, and product was extracted with CHCl₃. The organic extractswere dried (MgSO₄), treated with activated charcoal, filtered andstripped in vacuo to leave the title compound as a tan solid (4.97 g,91%).

EXAMPLE 22 ##STR94## Ethyl 8- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-2-carboxylate

By the method of Example 6, the product from Example 21 was dissolved inMEK (130 mL) and treated with NaI (3.4 g, 23 mmol) and triethylphosphite (5.32 g, 32 mmol). Final purification via flash chromatography(95/4.5/0.5 EtOAc/EtOH/Et₃ N) provided 3.23 g (45%) of title compound.

EXAMPLE 23 ##STR95## 8-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid (HCl)

Following the procedure for Example 7, the product from Example 22 (3.23g, 9.5 mmol) was combined with 4N. HCl (15 mL) to give 2.64 g of titlecompound as the HCl salt.

Analysis Calcd. for C₉ H₉ N₂ O₅ P+1.0 HCl+1.5 H₂ O (MW=319.64) C, 33.81;H, 4.10; N, 8.76. Found C, 33.47; H, 4.03; N, 8.62.

EXAMPLE 24 ##STR96## 5-chloro-6-methyl-2-pyridinamine

This compound was prepared according to the procedure of Kress, et.al.,J. Org. Chem., 1976, (41), 93.

EXAMPLE 25 ##STR97##2-(5-chloro-6-methyl-2-pyridinyl)-1H-isoindole1,3(2H)-dione

By the method of Example 32, the product from Example 24 (5.0 g, 35mmol) was reacted with phthalic anhydride (5.19 g, 35 mmol). Finalworkup produced 8.18 g (86%) of the title compound.

EXAMPLE 26 2-6-(bromomethyl)-5-chloro-2-pyridinyl!-1H-isoindole-1,3(2H)-dione##STR98##

Following the procedure of Example 2, the product from Example 25 (6.07g, 22 mmol) was reacted with NBS (3.96 g, 22 mmol) in CH₂ Cl₂ (150 mL).The crude title product (8.98 g, >100%) was obtained and used withoutfurther purification.

EXAMPLE 27 ##STR99## Diethyl3-chloro-6-(1,3-dihydro-1,3-dioxo-2Hisoindol-2-yl)-2-pyridinyl!methyl!phosphonate

The product from Example 26 was dissolved in MEK (180 mL) and placed ina 500 mL flask under a N₂ atmosphere. Sodium iodide (catalytic) wasadded to the reaction which was subsequently stirred at room temperaturefor 20 min. Triethyl phosphite (3.66 g, 22 mmol) was added to thereaction. The reaction was heated to reflux for 6 h, cooled to roomtemperature, and stirred an additional 16 h. The reaction was filteredand all solvent removed in vacuo to yield the crude title compound.Purification via flash chromatography (96/4 CHCl₃ /EtOH) produced thepure title product.

EXAMPLE 28 ##STR100## Diethyl(6-amino-3-chloro-2-pyridinyl)methyl!phosphonate

Following the procedure from Example 16, the product from Example 27(1.0 g, 2.4 mmol) was reacted with hydrazine monohydrate (0.121 g, 2.4mmol) in CH₂ Cl₂ (25 mL). Workup produced the crude title product whichwas used without further purification.

EXAMPLE 29 ##STR101## Ethyl 6-chloro-5-(diethoxyphosphinyl)methyl!imidazo 1,2-a!pyridine-2-carboxylate

Following the procedure for Example 17, the residue from Example 28 wascombined with ethyl bromopyruvate (0.468 g, 2.4 mmol) in DME (25 mL).After the resulting salt was refluxed in abs EtOH (30 mL) for 6 h,workup and puricication produced 0./114 g (13% of title compound).

Analysis Calcd. for C₁₅ H₂₀ N₂ O₅ Pcl (MW=374.76) C, 48.07; H, 5.38; N,7.47. Found C, 47.82; H, 5.30; N, 7.41.

EXAMPLE 30 ##STR102## 6-chloro-5-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid

Following the procedure in Example 7, the product from Example 29 wasrefluxed in 4N. HCl (7 mL) for 7 h. Workup produced the title productHCl salt.

Analysis Calcd. for C₉ H₈ N₂ O₅ PCl+1.0 H₂ O (MW=308.62) C, 35.03; H,3.27; N, 9.08. Found C, 34.93; H, 3.36; N, 8.93.

EXAMPLE 31 ##STR103## 4-hydroxy-6-methyl-2-pyridinamine

Concentrated ammonium hydroxide (NH₄ OH, 1.2 L) and4-hydroxy-6-methyl-2-pyrone (148 g, 1.17 mol) were combined in a Parrbomb. The bomb was shaken and heated to 200° C. for 20 h. After coolingthe bomb to room temperature, the heterogeneous reaction mixture wasfiltered. The solid product residue was washed with water and Et₂ Obefore it was dissolved in boiling MeOH, decolorized with accivatedcharcoal, and crystallized. Three crops of analytically pure titlecompound were obtained (84.3 g, 57.8%).

Analysis Calcd for C₆ H₈ N₂ O (MW=124.14) C, 58.05; H, 6.50; N, 22.57.Found C, 57.72; H, 6.63; N, 22.63.

EXAMPLE 32 ##STR104##2-(4-hydroxy-6-methyl-2-pyridinyl)-1H-isoindole-1,3(2H)-dione

The title compound from Example 31 (2.5 g, 20.0 mmol) and phthalicanhydride (3.0 g, 20.0 mmol) were ground in a mortor. This mixture wasadded to a flask which was flushed with N₂ and immersed in an oil bathmaintained at 190° C. Heating was continued for 2 h while a gentle flowof N₂ was passed through the flask to removed the water by-product. Thereaction was cooled to room temperature and the product solid wasfiltered and washed extensively with 100 mL aliquotes of CH₂ Cl₂, MeOH,EtOAc, and Et₂ O. After drying, 4.63 g (92%) of the title material wasobtained.

Analysis Calcd. for Cl₄ H₁₀ N₂ O₃ (MW=254.25) C, 66.14; H, 3.96; N,11.02. Found C, 65.81; H, 4.02; N, 10.95.

EXAMPLE 33 ##STR105##2-(4-chloro-6-methyl-2-pyridinyl)-1H-isoindole-1,3(2H)dione

The title compound from Example 32 is heated at 200° C. with excessphosphorusoxychloride (POCl₃) under an Ar atmosphere. The reactionmixture is poured into ice water and this solution is extracted with Et₂O. After washing with saturated potassium carbonate (K₂ CO₃), thesolution is dried and stripped of all solvent to give the desiredcompound.

EXAMPLE 34 ##STR106## 2-6-(bromomethyl)-4-chloro-2-pyridinyl!-1H-isoindole-1,3(2H)-dione

The title material is prepared from the ; title product of Example 33 bythe method of Example 2.

EXAMPLE 35 ##STR107## Diethyl4-chloro-6-(1,3-dihydro-1,3-dioxo-2H-isoindol2-yl)-2-pyridinyl!methyl!phosphonate

The title material is synthesized from the title product of Example 34by the method of Example 27.

EXAMPLE 36 ##STR108## Diethyl(6-amino-4-chloro-2-pyridinyl)methyl!phosphonate

The title compound is prepared from the title product of Example 35 bythe method of Example 16.

EXAMPLE 37 ##STR109## Ethyl 7-chloro-5-(diethoxyphosphinyl)methyl!imidazo 1,2-a!pyridine-2-carboxylate

The title material is synthesized from the title product of Example 36by the method of Example 17.

EXAMPLE 38 ##STR110## 7-chloro-5-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid

The title compound is prepared from the title product of Example 37 bythe method of Example 7.

EXAMPLE 39 ##STR111##2-(4-methoxy-6-methyl-2-pyridinyl)-1H-isoindole-1,3(2H)-dione

The title material from Example 32 (4.32 g, 17.1 mmol) was combined withK₂ CO₃ (2.37 g, 17.1 mmol), methyl iodide (2.4 g, 17.1 mmol), and 40 mLof acetone. This heterogeneous mix was stirred at room temperature fortwo weeks before it was suction filtered and the solid washed with waterand Et₂ O. The residue white solid is the desired title product.

EXAMPLE 40 ##STR112## 2-6-(bromomethyl)-4-methoxy-2-pyridinyl!-1Hisoindole-1,3(2H)-dione

The title compound is prepared from the title product of Example 39 bythe method of Example 2.

EXAMPLE 41 ##STR113## Diethyl6-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)4-methoxy-2-pyridinyl!methyl!phosphonate

The title material is synthesized from the title product of Example 40by the method of Example 27.

EXAMPLE 42 ##STR114## Diethyl(6-amino-4-methoxy-2-pyridinyl)methyl!phosphonate

The title compound is prepared from the title product of Example 41 bythe method of Example 16.

EXAMPLE 43 ##STR115## Ethyl 5-(diethoxyphosphinyl)methyl!-7-methoxyimidazo1,2-a!pyridine-2-carboxylate

The title material is synthesized from the title product of Example 42by the method of Example 17.

EXAMPLE 44 ##STR116## 7-methoxy-5-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid

The title material is prepared from the title product of Example 43 bythe method of Example 7.

EXAMPLE 45 ##STR117##N-(3-bromo-6-methyl-2-pyridinyl)-2,2-dimethylpropanamide

Carbontetrachloride (CCl4, 300 mL) and the product of Example 1 (50.6 g,0.26 mol) were added to a 1 L flask equipped with a N₂ inlet Thesolution was stirred until all solid dissolved. N-bromo-succinimide(NBS, 46.8 g, 0.26 mol) was then added to the reaction flask, followedby 2,2'-azobisisobutyronitrile (AIBN, 0.02 g). The reaction was heatedto reflux for 6 h with a 500 watt reflector spot lamp. An additional 0.5eq (23.4 g) of NBS was added to the reaction, and refluxing wascontinued for 2 h. After cooling the reaction to room temperature, itwas filtered and all solvent was removed under reduced pressure. Flashchromatography (15/85 EtOAc/Hex) provided 31.6 g (47%) of title productand 22.2 g (33%) of the title material of Example 2.

EXAMPLE 46 ##STR118## 3-bromo-6-methyl-2-pyridinamine

Following the procedure from Example 3, the product from Example 45(26.1 g, 96 mmol) was refluxed in 10% (v/v) H₂ SO₄ (200 mL) to produce11.14 g (62%) of title compound.

EXAMPLE 47 ##STR119## Ethyl8-bromo-5-methylimidazo*1,2-a*pyridine-2-carboxylate

Following the procedure for Example 6, the product from Example 46(11.14 g, 60 mmol) was reacted with ethyl bromopyruvate (11.7 g, 60mmol) in DME (100 mL). After the isolated salt was refluxed in abs EtOH(100 mL) for 2 h, 6.9 g (41%) of the title product was obtained.

Analysis Calcd. for C₁₁ H₁₁ N₂ O₂ Br (MW=283.13) C, 46.67; H, 3.92; N,9.89. Found C, 46.39; H, 3.88; N, 9.82.

EXAMPLE 48 ##STR120## Ethyl 8-(diethoxyphosphinyl)-5-methylimidazo1,2-a!-pyridine-2-carboxylate

Toluene (10 mL) was placed in a 25 mL 3-neck flask equipped with acondensor, Ar inlet and stopper. The product from Example 47 (0.736 g,2.6 mmol), diethylphosphite (1.1 g, 7.8 mmol) and Et₃ N (0.8 g, 7.8mmol) were placed in the flask, which was then heated to 80° C.Tetrakis(triphenylphosphine) Palladium(O) Pd (0), 0.4 g, 0.35 mmol! wasadded to the reaction and heating was continued for 22 h at which pointan additional 0.12 g of Pd(O) was added to the reaction. Heating wascontinued for an additional 7 h. The reaction was cooled to roomtemperature and stirred 50 h. Diethyl ether was added to the reaction todissolve the salts which had formed. Purification via a chromatotron(97/2.5/0.5 CH₂ Cl₂ /EtOH/NH₄ OH) provided 0.06 g (7%) of title product.

EXAMPLE 49 ##STR121## 5-methyl-8-phosphonoimidazo1,2-a!pyridine-2-carboxylic acid, hydrochloride

The title material was prepared from the product of Example 48 by themethod of Example 7.

Analysis Calcd. for C₉ H₉ N₂ O₅ P+1.1 H₂ O+0.75 HCl (MW=303.319): C,35.64; H, 3.97; N, 9.24; Cl, 8.77. Found: C, 35.35; H, 3.96; N, 8.96 Cl,9.07.

EXAMPLE 50 ##STR122## Ethyl 5-bromoimidazo 1,2-a!pyridine-2-carboxylate

Ethylene glycol dimethylether (DME, 80 mL) and 2-bromo-5-aminopyridine(5 g, 28.9 mmol) were combined in a flask under N₂. After stirring thismixture for 20 min, ethyl bromopyruvate (6.75 g, 34.6 mmol) was addedand the reaction was allowed to stir at room temperature for 16 h. Thereaction was completed following the procedure of Example 4 to give 6.4g (82%) of the title product.

Analysis Calcd. for C₁₀ H₉ N₂ O₂ Br (MW=269.10) C, 44.63; H, 3.37; N,10.41; Br, 29.69. Found C, 44.38; H, 3.34; N, 10.54; Br, 28.39.

EXAMPLE 51 ##STR123## Ethyl 5-(diethoxyphosphinyl)imidazo1,2-a!pyridine-2-carboxylate

The product from Example 50 (4.0 g, 14.9 mmol), diethylphosphite (6.28g, 45.5 mmol) Et₃ N (4.51 g, 45.5 mmol) and toluene (20 mL) werecombined in a flask equipped with a N₂ inlet, condensor and stopper.After heating this mixture to 75° C., tetrakis(triphenylphosphine)Palladium(O) 2.3 g, 2.0 mmol! was added and the reaction was heated at90° C. for 2 h. The reaction was cooled to room temperature, dilutedwith Et₂ O, and filtered. The filtrate was concentrated and 2.1 g (39%)of the title product was isolated by high performance liquidchromatography (HPLC).

EXAMPLE 52 ##STR124## Ethyl 5-(diethoxyphosphinyl)imidazo1,2-a!pyridine-2-carboxylate, monohydrochloride

The product from Example 51 (1.6 g, 4.4 mmol) was dissolved in CH₂ Cl₂(30 mL), treated with activated charcoal and filtered. To this filtratewas then added 6N HCl in dioxane (0.9 mL, 4.4 mmol) followed by Et₂ O(100 mL). The precipitated product was filtered, washed with Et₂ O, anddried in vacuo.

Analysis calcd. for C₁₄ H₁₉ N₂ O₅ P+0.9 HCl+1 H₂ O (MW=377.12) C, 44.59;H, 5.85; N, 7.43. Found C, 4.44; H, 5.46; N, 7.96.

EXAMPLE 53 ##STR125## 5-phosophonoimidazo 1,2-a!pyridine-2-carboxylicacid, hydrochloride

The title material was synthesized from the title product of Example 52by the method of Example 7.

Analysis Calcd. for C₈ H₇ N₂ O₅ P+0.5 H₂ O+0.05 HCl (MW=252.96); C,37.99; H, 3.21; N, 11.07; Cl, 0.7. Found: C, 38.00; H, 2.99; N, 11.14;Cl, 0.54.

EXAMPLE 54 ##STR126## Ethyl 5-formylimidazo 1,2-a!pyridine-2-carboxylate

Pyridinium chlorochromate (7.3 g, 33.8 mmol, Aldrich) and CH₂ Cl₂ (100mL) were added to a 300 mL beaker. This mixture was stirred until allsolid had dissolved. The product from Example 4 (5.0 g, 22.7 mmol) wasthen added to the beaker and the mixture was stirred at room temperaturefor 2 h. Another 100 mL of CH₂ Cl₂ was added before this mixture wasfiltered. The gummy residue was washed extensively until it became asolid. The combined filtrate was stripped of all solvent and the residuewas flash chromatographed (10/89.2/0.2 acetone/CH₂ Cl₂ /Et₃ N) toprovide 3.3 g (67%) of the title material.

EXAMPLE 55 ##STR127## Ethyl 5- (diethoxyphosphinyl)hydroxymethyl!imidazo1,2-a!pyridine-2-carboxylate

Diethyl phosphite (1.7 g, 12.3 mmol, Aldrich), N,N-diisopropylethylamine(1.63 g, 12.4 mmol, Aldrich) and toluene (60 mL) were combined in a 100mL flask equipped with a N₂ inlet and condensor. After warming thissolution to 60° C., the product from Example 54 was added. Afterstirring at 75°-80° C. for 3 h, all solvent was removed from thismixture and the residue was chromatographed (7.5/92.4/0.1isopropanol/CH₂ Cl₂ /HOAc) to give 1.2 g (66%) of the title product.

EXAMPLE 56 ##STR128## Ethyl 5- (diethoxyphosphinyl)hydroxymethyl!imidazo1,2-a!pyridine-2-carboxylate, monohydrochloride

The product from Example 55 (1.2 g, 3.37 mmol) was dissolved in CH₂ Cl₂(15 mL) and treated with 6N HCl in dioxane (0.56 mL, 3.37 mmol). Theresulting salt was precipitated with Et₂ O, filtered, washed with Et₂ O,and dried in vacuo to give 1.3 g (99%) of the title product.

Analysis Calcd. for C₁₅ H₂₁ N₂ O₆ P+HCl+0.25 H₂ O (MW=397.28) C, 45.35;H, 5.58; N, 7.05, Cl, 8.92. Found C, 45.38; H, 5.58; N, 6.94; Cl, 9.03.

EXAMPLE 57 ##STR129## 5-(hydroxyphosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid, monohydrochloride

The title compound was synthesized from the title material of Example 56(0.2 g, 0.5 mmol) and 50 mL of 4N HCl by the procedure of Example 7. A50 mg sample of the product salt was obtained.

Analysis Calcd. for C₉ H₉ N₂ O₆ P+HCl (MW=308.61) C, 35.03; H, 3.27; N,9.08, Cl, 11.49. Found C, 35.07; H, 3.63; N, 8.57; Cl, 11.41.

EXAMPLE 58 ##STR130## 5-(phosphonocarbonyl)imidazo1,2-a!pyridine-2-carboxylic acid, monohydrochloride

The title material is prepared by oxidizing the product of Example 57with periodinane in CH₂ Cl₂.

EXAMPLE 59 ##STR131## Ethyl 5- (diethoxyphosphinyl)fluoromethyl!imidazo1,2-a!pyridine-2-carboxylate, monohydrochloride

The title material was synthesized by the reaction of the title productof Example 55 with diethylaminosulphur trifluoride (DAST) in CH₂ Cl₂using the method of Blackburn, G. M.; Kent, D. E. J. Chem. Soc., Chem.Comm. 1981, 511-513.

Analysis Calcd. for C₁₅ H₂₀ N₂ O₅ PF+0.5 H₂ O+1.0 HCl (MW=403.778): C,44.62; H, 5.49; N, 6.94; F, 4.71. Found: C, 44.28; H, 5.32; N, 7.16; F,4.91.

EXAMPLE 60 ##STR132## 5- (diethoxyphosphinyl)fluoromethyl!imidazo1,2-a!pyridine-2-carboxylic acid, monohydrochloride

The title product was obtained from the title material of Example 59 bythe method of Example 7.

Analysis Calcd. for C₉ H₈ N₂ O₅ PF+1.0 H₂ O+0.55 HCl (MW=312.22): C,34.62; H, 3.41; N, 8.97; Cl, 6.25. Found: C, 34.39; H, 3.02; N, 8.92;Cl, 6.30.

EXAMPLE 61 ##STR133## Ethyl 5- 2-(diethoxyphosphinyl)-E-ethenyl!imidazo1,2-a!pyridine-2-carboxylate

Tetraethyl methylenediphosphonate (Lancaster) in benzene was added to abenzene solution of sodium hydride (NaH). The product from Example 54,also dissolved in benzene, was then added dropwise to the reactionmixture. After stirring the resulting mixture for 2 h under an Aratmosphere, the reaction was diluted with CHCl₃ /H₂ O (2/1). The CHCl₃layer was separated and the aqueous layer extracted with CHCl₃.Chromatography of the residue after removal of all solvent from thecombined extracts gave the title product.

Analysis Calcd. for C₁₆ H₂₁ N₂ O₅ P+0.7 H₂ O (MW=364.941): C, 52.66; H,6.19; N, 7.68. Found: C, 52.79; H, 6.13; N, 7.35.

EXAMPLE 62 ##STR134## 5-(2-phosphono-E-ethenyl)imidazo1,2-a!pyridine-2-carboxylic acid, hydrochloride

The title material was synthesized from the title product of Example 61by the method of Example 7.

Analysis Calcd. for C₁₀ H₉ N₂ O₅ P+0.6 H₂ O+0.5 HCl (MW=297.206): C,40.41; H, 3.63; N, 9.43; Cl, 5.96. Found: C, 40.20; H, 3.54; N, 9.21;Cl, 6.19.

EXAMPLE 63 ##STR135## 5-(2-phosphonoethyl)imidazo1,2-a!pyridine-2-carboxylic acid, hydrochloride

The title material was prepared by catalytic (Pd/C) hydrogenation of thetitle product of Example 62 under standard Parr conditions.

Analysis Calcd. for C₁₀ H₁₁ N₂ O₅ P+0.5 H₂ O+1.2 HCl (MW=322.944): C,37.19; H, 4.12; N, 8.67; Cl, 13.17. Found: C, 37.47; H, 4.29; N, 8.46;Cl, 12.87.

EXAMPLE 64 ##STR136## Ethyl 8-(hydroxymethyl)-3-methylimidazo1,2-a!pyridine-2-carboxylate

The title compound was synthesized by the method of Example 4. Theproduct from Example 19 (2.0 g, 16 mmol) was reacted with3-bromo-2-oxobutyric acid ethyl ester (3.7 g, 18 mmol) to give 2.85 g(76%) of title product.

EXAMPLE 65 ##STR137## Ethyl 8-(chloromethyl)-3-methylimidazo1,2-a!pyridine-2-carboxylate

The title material was synthesized from the title product of Example 64by the method of Example 5.

EXAMPLE 66 ##STR138## Ethyl 8-(diethoxyphosphinyl)methyl!-3-methylimidazo 1,2-a!pyridine-2-carboxylate

The title material was synthesized from the title product of Example 65by the method of Example 6.

Analysis Calcd. for C₁₆ H₂₃ N₂ O₅ P (MW=354.34) C, 54.23; H, 6.54; N,7090. Found C, 53.92; H, 6.66; N, 7.77.

EXAMPLE 67 ##STR139## 3-methyl-8-(phosphonomethyl)imidazo1,2-a!pyridine-2-carboxylic acid, monohydrochloride

The title material was synthesized from the title product of Example 66by the method of Example 7.

Analysis Calcd. for C₁₀ H₁₁ N₂ O₅ P+0.8 H₂ O (MW=313.76) C, 38.28; H,4.30; N, 8.930 Found C, 38.39; H, 4.09; N, 9.06.

EXAMPLE 68 ##STR140## Ethyl 5-(hydroxymethyl)imidazo1,2-a!pyridine-3-carboxylate

The title product is prepared by the reaction of the title compound fromExample 3 with ethyl a-chloroformylacetate by the method of Example 4 orin dioxane by the procedure of W. W. Paudley; R. A. VanDahm; Y. N. Park,J. Heterocyclic Chem., 1972, (9), 81-85.

EXAMPLE 69 ##STR141## Ethyl 5-(chloromethyl)imidazo1,2-a!pyridine-3-carboxylate

The title material is synthesized from the title product of Example 68by the method of Example 5.

EXAMPLE 70 ##STR142## Ethyl 5- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-3-carboxylate

The title product is obtained from the title material of Example 69 bythe method of Example 6.

EXAMPLE 71 ##STR143## 5-(phosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title product is prepared from the title material of Example 70 bythe method of Example 7.

EXAMPLE 72 ##STR144## Ethyl 6-(hydroxymethyl)imidazo1,2-a!pyridine-3-carboxylate

The title material is synthesized from the title material of Example 9by the methods suggested in Example 68.

EXAMPLE 73 ##STR145## 6-(phosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title product is prepared from the title material of Example 72 bythe successive application of the methods of Examples 5, 6, and 7.

EXAMPLE 74 ##STR146## Ethyl 8-(hydroxymethyl)imidazo1,2-a!pyridine-3-carboxylate

The title product is prepared from the title material of Example 19 bythe methods suggested in Example 68.

EXAMPLE 75 ##STR147## 8-(phosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title material is synthesized from the i title material of Example74 by the successive application of the methods of Examples 5, 6, and 7.

EXAMPLE 76 ##STR148## Ethyl 7- (diethoxyphosphinyl)methyl!imidazo1,2-a!pyridine-3-carboxylate

The title product is generated from the title material of Example 16 bythe methods suggested in Example 68.

EXAMPLE 77 ##STR149## 7-(phosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title product is prepared from the title 5 material of Example 76 bythe method of Example 7.

EXAMPLE 78 ##STR150## Ethyl 6- chloro-5-(diethoxyphosphinyl)methyl!imidazo 1,2-a!pyridine-3-carboxylate

The title product is obtained from the title material of Example 28 bythe method of Example 17 or the procedures suggested in Example 68.

EXAMPLE 79 ##STR151## 6-chloro-5-(phosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title compound is prepared from the i title material of Example 78by the method of Example 7.

EXAMPLE 80 ##STR152## Ethyl 5-(diethoxyphosphinyl)methyl!-7-methoxyimidazo1,2-a!pyridine-3-carboxylate

The title compound is synthesized from the title material of Example 42by the method of Example 17 or the procedures suggested in Example 68.

EXAMPLE 81 ##STR153## 7-methoxy-5-(phosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title compound is synthesized from the title material of Example 80by the method of Example 7.

EXAMPLE 82 ##STR154## Ethyl 7-chloro-5-(diethoxyphosphinyl)methyl!imidazo- 1,2-a!pyridine-3-carboxylate

The title material is synthesized from the title compound of Example 36by the method of Example 17 or the procedures suggested in Example 68.

EXAMPLE 83 ##STR155## 7-chloro-5-(phosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title compound is prepared from the title material of Example 82 bythe method of Example 7.

EXAMPLE 84 ##STR156## Ethyl 8-(diethoxyphosphinyl)-5-methylimidazo1,2-a!pyridine-3-carboxylate

The title material is obtained from the title compound of Example 46 bysuccessive application of the methods suggested in Example 68 andExample 48.

EXAMPLE 85 ##STR157## 5-methyl-8-phosphonoimidazo1,2-a!pyridine-3-carboxylic acid

The title product is synthesized from the i title material of Example 84by the method of Example 7.

EXAMPLE 86 ##STR158## Ethyl 5-bromoimidazo 1,2-a!pyridine-3-carboxylate

The title material is obtained from 2-bromo5-aminopyridine by the methodof Example 50 or the procedures suggested in Example 68.

EXAMPLE 87 ##STR159## Ethyl 5-(diethoxyphosphinyl)imidazo1,2-a!pyridine-3-carboxylate

The title product is synthesized from the title material of Example 86by the method of Example 51.

EXAMPLE 88 ##STR160## 5-phosphonoimidazo 1,2-a!pyridine-3-carboxylicacid

The title compound is prepared from the title material of Example 87 bythe method of Example 7.

EXAMPLE 89 ##STR161## Ethyl 5-formylimidazo 1,2-a!pyridine-3-carboxylate

The title material is synthesized from the title product of Example 68by the method of 5 Example 54.

EXAMPLE 90 ##STR162## Ethyl 5- 2-(diethoxyphosphinyl)-E-ethenyl!imidazo-1,2-a!pyridine-3-carboxylate

The title compound is prepared from the O title material of Example 89by the method of Example 61.

EXAMPLE 91 ##STR163## 5-(2-phosphono-E-ethenyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title material is prepared from the title product of Example 90 bythe method of Example 7.

EXAMPLE 92 ##STR164## 5-(2-phosphonoethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title compound is generated from the title material of Example 91 bythe method of Example 63.

EXAMPLE 93 ##STR165## Ethyl 5-(diethoxyphosphinyl)hydroxymethyl!imidazo- 1,2-a!pyridine-3-carboxylate

The title product is prepared from the title 5 material of Example 89 bythe method of Example 55.

EXAMPLE 94 ##STR166## 5-(hydroxyphosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title material is prepared from the .0 title product of Example 93by the method of Example 7.

EXAMPLE 95 ##STR167## 5-(fluorophosphonomethyl)imidazo1,2-a!pyridine-3-carboxylic acid

The title material is synthesized from the title product of Example 93by the successive application of the methods of Examples 59 and 7.

EXAMPLE 96 ##STR168## Ethyl 6-(diethoxyphosphinyl)imidazo1,2-a!pyridine-2-carboxylate

The title material was synthesized from ethyl 6-bromoimidazo1,2-a!pyridine-2-carboxylate following the procedure for Example 51.

Analysis Calcd. for C₁₄ H₁₉ N₂ O₅ P (MW=326.289): C, 51.54; H, 5.87; N,8.58; P, 9.49. Found: C, 51.80; H, 5.93; N, 8.41; P, 9.28.

EXAMPLE 97 ##STR169## 6-phosphonoimidazo 1,2-a!pyridine-2-carboxylicacid

The title material was synthesized in 82% yield from the title productof Example 96 following the procedure for Example 53.

Analysis Calcd. for C₈ H₇ N₂ O₅ P+0.75 H₂ O (MW=255.64): C, 37.59; H,3.35; N, 10.96; P, 12.12. Found: C, 37.87; H, 3.11; N, 11.03; P, 12.16.

EXAMPLE 98 ##STR170## Ethyl 5- 2-(diethoxyphosphinyl)ethyl!imidazo1,2-a!pyridine-2-carboxylate

The title material was prepared by catalytic (Pd/C) hydrogenation of thetitle product of Example 61 under standard Parr conditions.

Analysis Calcd. for C₁₆ H₂₃ N₂ O₅ P (MW=354.346): C, 54.23; H, 6.54; N,7.91. Found: C, 54.18; H, 6.81; N, 7.84.

EXAMPLE 99 ##STR171## Ethyl 5-(cyanomethyl)imidazo1,2-a!pyridine-2-carboxylate

Title material is made by dissolving the title product of Example 5 inDMF and after cooling to 0° C., reacting with KI and KCN. The reactionis stirred for 6 h at 0° C. After warming to room temperature, titlecompound is obtained by diluting with CHCl₃, washing with water, andremoving all solvent in vacuo.

EXAMPLE 100 ##STR172## Ethyl 5-(1H-tetrazol-5-ylmethyl)imidazo1,2-a!pyridine-2-carboxylate

The title material is prepared by heating the title product of Example99 with azido tributylstannane at 80° C. for 72 h. After cooling to roomtemperature, the reaction is treated with methanolic HCl for 30 min.,diluted with 4N HCl, washed with diethyl ether and concentrated to yieldtitle material.

EXAMPLE 101 ##STR173## 5-(1H-tetrazol-5-ylmethyl)imidazo1,2-a!pyridine-2-carboxylic acid

The title material is prepared from the title product of Example 100 bythe method of Example 7.

EXAMPLE 102 ##STR174## Ethyl 5-3-(diethoxyphosphinyl)-2-propenyl!imidazo 1,2-a!pyridine-2-carboxylate

The title material is made from ethyl 5-(2-oxoethyl)imidazo1,2-a!pyridine-2-carboxylate by the method in Example 61.

EXAMPLE 103 ##STR175## 5-(3-phospono-2-propenyl)imidazo1,2-a!pyridine-2-carboxylic acid

The title material is synthesized from the title product of Example 102by the method of Example 7.

EXAMPLE 104 ##STR176## Ethyl 5- 3-(diethoxyphosphinyl)propyl!imidazo1,2-a!pyridine-2-carboxylate

The title material is prepared by catalytic (Pd/C hydrogenation of thetitle product of Example 102 under standard Parr conditions.

EXAMPLE 105 ##STR177## 5-(3-phosponopropyl)imidazo1,2-a!pyridine-2-carboxylic acid

The title material is synthesized from the title product of Example 104by the method of Example 7.

BIOLOGICAL EVALUATION NMDA-Selective Glutamate Binding Assay

Synaptic plasma membranes (SPM) were prepared as previously describedMonahan, J. B. and Michel, J., "Identification and Characterization ofan N-methyl-D-aspartate-specific L ³ H!glutamate Recognition Site inSynaptic Plasma Membranes, J. Neurochem., 48, 1699-1708 (1987)!. The SPMwere stored at a concentration of 10-15 mg/ml in 0.32M sucrose, 0.5 mMEDTA, 1mM MgSO₄, 5 mM Tris/SO₄, pH 7.4, under liquid nitrogen. Theidentity and purity of the subcellular fractions were confirmed by bothelectron microscopy and marker enzymes. Protein concentrations weredetermined by using a modification of the method of Lowry Ohnishi, S. T.and Barr, J. K., "A Simplified Method of Quantitating Proteins Using theBiuret and Phenol Reagents", Anal. Biochem., 86, 193-197 (1978)!. TheSPM were treated identically for the ³ H!AMPA (QUIS), ³ H!kainate andsodium-dependent L- ³ H!-glumatate binding assays. The SPM were thawedat room temperature, diluted twenty-fold with 50 mM Tris/acetate, pH7.4, incubated at 37° C. for 30 minutes, and centrifuged at 100,000 gfor 15 minutes. The dilution, incubation, and centrifugation wasrepeated a total of three times. Prior to use in the NMDA specific L- ³H!-glutamate binding assay the SPM were thawed, diluted twenty fold with50 mM Tris/acetate, pH 7.4 containing 0.04% (v/v) Triton X-100,incubated for 30 minutes at 37° C. and centrifuged as described above.The Triton X-100 treated membranes were washed with 50 mM Tris/acetate,pH 7.4 and centrifuged at 100,000 g for 15 minutes a total of fourtimes. Triton X-100 treatment of the SPM resulted in a higher affinityand more consistency in this L- ³ H!glutamate binding assay. For thisreason the K_(d) for glutamate and the K_(i) values for other compoundsare lower than previously reported; however, the pharmacological profileof this binding site was unaltered. The basic procedure for the receptorsubclass binding assays was similar. This general method involved addingthe radioligand (12.5 nM L- ³ H!glutamate; 0.5 nM ³ H!kainate or 10 nM ³H!AMPA) to the appropriate concentration of the test compound andinitiating the assay by the addition of ice cold synaptic plasmamembranes (0.2-0.45 mg). The binding assays were performed in 1.5 mLcentrifuge tubes with the total volume adjusted to 1.0 mL. Additions oftest compounds were made in 50 mM Tris/acetate, pH 7.4 and incubationswere carried out at 0°-4° C. The incubation time for the NMDA and theAMPA binding assays was 10 minutes, for the kainate binding assay 60minutes and for the sodium-dependent glutamate binding assay 15 minutes.The AMPA binding assay contained 100 mM KSCN and the sodium-dependentglutamate binding assay contained 150 mM sodium acetate in addition tothe previously described reagents. To terminate the incubation, thesamples were centrifuged for 15 minutes at 12,000 g and 4° C. in aBeckman Microfuge 12. The supernatant was aspirated and the pelletedmembranes dissolved in Beckman BTS-450 tissue solubilizer for a minimumof 6 hours at room temperature. Beckman MP scintillation cocktailcontaining 7 mL/l acetic acid was then added and the samples counted ona Beckman LS 5800 or 3801 liquid scintillation counter with automaticcorrections for quenching and counting efficiency. Nonspecific bindingwas defined as the residual binding in the presence of either excessL-glutamate (0.1-0.4 mM), kainate (0.01 mM), or NMDA (0.5 mM), and was15-25% of the total binding in the NMDA binding assay, 19-27% in theAMPA binding assay, 20-30% in the kainate binding assay and 10-15% inthe sodium-dependent binding assay. Radioligand binding to the synapticplasma membranes was analyzed using Scatchard and Hill transformationsand the K_(i) values of the compounds determined using logit-logtransformations. Calculations and regression analysis were performedusing templates developed for Lotus 1, 2, 3 as previously describedPullan, L. M. "Automated Radioligand Receptor Binding Analysis withTemplates for Lotus", Computer Appln. Biosci., 3, 131 (1987)!. Bindingresults are reported in Table I for example compounds of the invention.

                  TABLE I                                                         ______________________________________                                        NMDA Receptor Binding Data                                                    Compound      K.sub.i IC.sub.50 Binding (μM)                               Ex. #         NMDA       KA        AMPA                                       ______________________________________                                         7            2.4        123       >300                                       13            >100       >300      >300                                       18            >100       >300      >300                                       23            4.5        >300      >300                                        23*          10.5                                                            30            >100       >300      >300                                       53            >10                                                             49            >10                                                             57            5.8        89        >300                                       67            >100       >300      >300                                       ______________________________________                                         *Second batch                                                            

TCP Modulation Assay

The effect on the TCP (1- 1-(2-thienyl)cyclohexyl!piperidine) bindingwas measured in rat brain synaptic membranes (SPM) prepared aspreviously described J. B. Monahan & J. Michel; J. Neurochem.48:1699-1708 (1987)!. Prior to their use in the binding assay, frozenSPM were thawed, diluted twenty fold with 50 mM Tris/acetate (pH 7.4containing 0.04% (v/v) Triton X-100), incubated for 30 min. at 37° C.and centrifuged at 95,000×g for 15 min. The Triton X-100 treated SPMwere washed with 5 mM Tris/HCl, pH 7.4 and centrifuged a total of sixtimes. The compound of Example #7 was incubated at differentconcentrations with SPM (0.2-0.4 mg protein) and 2 nM tritiated TCP, ina total volume of 0.5 ml of 5 mM Tris/HCl buffer pH 7.4 at 25° C. for 60min. The samples were filtered through glass fiber filters (Schleicher &Schuell #32) which have been pretreated with 0.05% (v/v)polyethylenimine, washed 4 times with 2 ml of ice-cold 5 mM Tris/HClbuffer, and then counted on a Beckman LS 5800 liquid scintillationcounter with automatic corrections for quenching and countingefficiency. Inhibition of TCP binding was measured as a decrease in thebinding in the presence of 0.05 mM L-glutamate. Non-specific binding wasdefined as the residual binding in the presence of 60 mM phencyclidine.Results are shown in Table II.

                  TABLE II                                                        ______________________________________                                        TCP Binding Data                                                              Compound Ex. # TCP K.sub.i IC.sub.50 (μM)                                  ______________________________________                                         7              3.2                                                           23             14.0                                                            23*            7.7                                                           57             (antag.)                                                       ______________________________________                                         *second batch                                                            

Forebrain Ischemia Assay

This assay was used to determine the extent of protection afforded bycompound of the invention to neural brain cells subjected to ischemicconditions. Male Mongolian gerbils, 50-70 gm, were used as subjects.Compound No. 7 (30 mg/kg) was injected i.p. 30 minutes prior to carotidocclusion into 6 gerbils at two different doses (300 mg/kg and 500mg/kg). In preparation for surgical procedures, the animals were lightlyanesthetized with methoxyflurane and placed upside down on a heated padwith their snout within a nosecone. A 70:30 mixture of nitrous oxide andoxygen containing 0.5% halothane was circulated through the nosecone toprovide continuous anesthesia throughout the surgical procedure. Amidline incision was made in the neck and the carotid arteries wereexposed. A length of suture thread was placed under each carotid. Thethread was then tightened around each carotid and pressure applied tothe thread to insure flow was occluded. Flow was occluded for 4-5minutes and then the thread was removed. The carotids were visuallyinspected to confirm that reflow had occurred. The wound was then closedwith autoclips and the gerbils allowed to recover. Following surgery,the gerbils were kept alive for 7 days. They were anesthetized with 100mg/kg sodium pentobarbital and perfused transcardially with saline (withheparin) followed by buffered formalin. The brain was removed, trimmedand prepared for histological processing. Sections (10 microns) werestained with thionin. At 7 days following this type of transient globalforebrain ischemia, damaged neurons in the vulnerable CAl region of thehippocampus have degenerated and been cleared away by glia.Quantification of the resulting lesion is made by counting the pyramidalcell somata in a 0.5 mm length of CAl of the hippocampus on the sectioncorresponding to P 1.7 mm in the gerbil brain atlas.

Normal cell count in this region of the hippocampus in unoperatedgerbils is 146±2. The effects of compound of Ex. #7 were assessed bycomparing the number of neural cells found in the hippocampus ofsubjects treated with Ex. #7 compound with the cell number found in theappropriate control groups. The groups were compared by the Mann-WhitneyU test Elementary Applied Statistics, Wiley and Sons, New York (1965)!.The cell loss was significantly reduced in gerbils given compound of Ex.#7. Results are reported in Table III.

                  TABLE III                                                       ______________________________________                                                         Gerbil Ischemia Data                                         Compound         # of Neurons/Field                                           ______________________________________                                        Ex. #7 (500 mg/kg)                                                                             112.6                                                        CONTROL          17.0    p < 0.0001                                           Ex. #7 (300 mg/kg)                                                                             53.0                                                         CONTROL)         32.8    P < 0.05                                             ______________________________________                                    

Anticonvulsant Assay

This assay was used to determine the extent of in vivo protectionagainst convulsions afforded by compound of the invention to micesubjected to artifically-induced convulsive conditions. Naive male CD-1mice (20-30 grams body weight) from Charles River Laboratories, PortageMich. served as subjects. The mice had ad libitum access to food andwater prior to testing and were maintained on a 12 hour light/12 hourdark schedule with testing during the light portion of the cycle. Themice were tested for motor impairment by use of the inverted screen testapproximately 5 minutes prior to anticonvulsant testing. The invertedscreen apparatus was similar to that described by Coughenour et alPharmacol. Biochem. Behav. 6, 351-353 (1977)!. Mice were placed on 13×13cm pieces of #4 wire mesh screen which were mounted horizontally. Thescreens were then slowly inverted. Mice that failed to climb to the topsof the inverted screens within 60 seconds were considered to have amotor impairment. Tonic hindlimb extensor seizures were then produced byapplication of electroconvulsive shock through concave electrodes to theeyeballs. Both the eyeballs and the electrodes were moistened with 0.9%saline to improve conductivity. The ECS stimulus was generated by use ofa Grass model S48D stimulator with a Grass model CCUlA constant currentunit in series with the output. Stimulation consisted of 10 msec pulsesof a 60 pps single phase square wave for a duration of 200 msec. Thecurrent was held constant at 15 mA. Compound of Example #7 was suspendedin a vehicle of 0.9% saline with a few drops of PG-Tween added. PG-Tweenis a 1:1 mixture of propylene glycol and Tween 80. The Example #7compound or vehicle was administered s.c. in a volume of 10 ml/kg bodyweight 30 minutes prior to application of the ECS stimulus. Immediatelyafter ECS application, each mouse was observed for the presence orabsence of a tonic himdlimb extensor seizure. There were 10 mice in eachtreatment group. The compound of Example #7 protected against tonichindlimb extensor seizures in a dose-dependent fashion, and alsoimpaired motor function in a similar dose range. Results are reported inTable IV below.

                  TABLE IV                                                        ______________________________________                                        Anticonvulsant Activity                                                                    Protected from                                                                             Exhibiting Motor                                    Dose Compound s.c.                                                                         ECS (% of Mice)                                                                            Impairments (% of Mice)                             ______________________________________                                        O(vehicle)   5(n = 20)    10(n = 20)                                          Example #7 - 10 mg/kg                                                                      20           30                                                  Example #7 - 32 mg/kg                                                                      60           50                                                  Example #7 - 56 mg/kg                                                                      90           70                                                  Example #7 - 100 mg/kg                                                                     100          90                                                               ED.sub.50 = 21.8                                                                           ED.sub.50 = 24.6                                                 (95% CI 12.3-32.9)                                                                         (95% CI 7-45.7)                                     ______________________________________                                    

Assay for Effect on cGMP Levels in Cerebellum

The purpose of this assay is to determine the extent of in vivobioavailability and the potency as an NMDA antagonist of compound of theinvention as compared to known NMDA antagonists, namely,3(2-carboxypiperizine-4-yl)propyl-1-phosphonic acid (CPP˜ andcis-4-phosphonomethyl-2-piperidinecarboxylic acid (CGS 19755). MaleSwiss-Webster mice (17-24 g were injected sub-cutaneously (s.c.) withcompound of the invention and the known NMDA antagonist standards 30minutes prior to sacrifice by focussed microwave irradiation. Groupsconsisted of 7-10 mice. Compounds of Ex. #7 was dissolved in isotonicsaline and all compounds were administered in a volume of 0.2 ml permouse. Cerebella samples were extracted in IN HCl. Hydrochloric acid inextracts of the cerebellum were freeze-dried for assay of cGMP with acommercial RIA kit (NEN). Statistics (Dunett's t-test) were performed asdescribed previously P. L. Wood et al., Neurochem,, 19, 975-982 (1980)!.ED₅₀ values were calculated from log-logit transformation of thedose-response data. Results are reported in Table V.

                  TABLE V                                                         ______________________________________                                        Cerebellar cGMP Modulation                                                                 Decrease in cGMP                                                 Compound     ED.sub.50 (mg/kg, s.c.)                                          ______________________________________                                        Ex. #7       18.3                                                             CPP          7.4                                                              CGS 19755    1.0                                                              ______________________________________                                    

Compound of Ex. #7 was shown to be brain bioavailable by its ability todecrease levels of cGMP in mouse cerebellum. Also, compound of EX. #7was found to be in the same range of potency as the known NMDAantagonist CPP.

Administration of compounds within Formula I to humans can be by anytechnique capable of introducing the compounds into the bloodstream of ahuman patient, including oral administration, and by intravenous,intramuscular and subcutaneous injections.

Compounds indicated for prophylactic therapy will preferably beadministered in a daily dose generally in a range from about 0.1 mg toabout 100 mg per kilogram of body weight per day. A more preferreddosage will be a range from about 1 mg to about 100 mg per kilogram ofbody weight. Most preferred is a dosage in a range from about 1 to about50 mg per kilogram of body weight per day. A suitable dose can beadministered, in multiple sub-doses per day. These sub-doses may beadministered in unit dosage forms. Typically, a dose or sub-dose maycontain from about 1 mg to about 100 mg of active compound per unitdosage form. A more preferred dosage will contain from about 2 mg toabout 50 mg of active compound per unit dosage form. Most preferred is adosage form containing from about 3 mg to about 25 mg of active compoundper unit dose.

The active compound is usually administered in apharmaceutically-acceptable formulation, although in some acute-caresituations a compound of Formula I may be administered alone. Suchformulations may comprise the active compound together with one or morepharmaceutically-acceptable carriers or diluents. Other therapeuticagents may also be present in the formulation. Apharmaceutically-acceptable carrier or diluent provides an appropriatevehicle for delivery of the active compound without introducingundesirable side effects. Delivery of the active compound in suchformulations may be bY various routes including oral, nasal, topical,buccal and sublingual, or by parenteral administration such assubcutaneous, intramuscular, intravenous and intradermal routes.

Formulations for oral administration may be in the form of capsulescontaining the active compound dispersed in a binder such as gelatin orhydroxypropylmethyl cellulose, together with one or more of a lubricant,preservative, surface-active or dispersing agent. Such capsules ortablets may contain controlled-release formulation as may be provided ina dispersion of active compound in hydroxypropylmethyl cellulose.

Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules having one or more of the carriers or diluents mentioned foruse in the formulations for oral administration.

Although this invention has been described with respect to specificembodiments, the details of these embodiments are not to be construed aslimitations. Various equivalents, changes and modifications may be madewithout departing from the spirit and scope of this invention, and it isunderstood that such equivalent embodiments are part of this invention.

What is claimed is:
 1. A compound of Formula II ##STR178## wherein B is1H-tetrazol-5-yl; wherein each of Y_(m) and Y_(n) is a spacer groupindependently selected from one or more groups of the formula ##STR179##wherein each of R²⁷ and R²⁸ is independently selected from hydrido,alkyl having from one to five carbon atoms, cycloalkyl having from threeto ten carbon atoms, halo, haloalkyl wherein the alkyl portion thereofcontains from one to five carbon atoms, phenyl, benzyl, hydroxy,hydroxyalkyl wherein the alkyl portion thereof contains from one to fivecarbon atoms, alkoxy wherein the alkyl portion thereof contains from oneto five carbon atoms, phenoxy, alkoxyalkyl wherein the alkyl portionthereof contains from one to five carbon atoms, benzyloxy, cyano,alkanoyl wherein the alkyl portion thereof contains from one to fivecarbon atoms, ##STR180## wherein each of R¹, R², R³ and R⁴ isindependently selected from hydrido, alkyl having from one to fivecarbon atoms and phenyl; wherein R²⁷ and R²⁸ may be taken together toform oxo or exomethylene; wherein each of R²⁹ and R³⁰ is independentlyselected from hydrido, alkyl having from one to five carbon atoms,haloalkyl wherein the alkyl portion thereof contains from one to fivecarbon atoms, phenyl, hydroxyalkyl wherein the alkyl portion thereofcontains from one to five carbon atoms and alkoxyalkyl wherein the alkylportion thereof contains from one to five carbon atoms; wherein each ofm and n is a number independently selected from zero to three,inclusive;wherein each X and T is one or more groups independentlyselected from hydrido, alkyl having from one to five carbon atoms,cycloalkyl having from three to ten carbon atoms, cycloalkylalkylwherein the alkyl portion thereof contains from one to five carbon atomsand the cycloalkyl portion contains from three to ten carbon atoms,halo, haloalkyl wherein the alkyl portion thereof contains from one tofive carbon atoms, alkenyl, cycloalkenyl, alkynyl, phenyl, benzyl,hydroxy, hydroxyalkyl wherein the alkyl portion thereof contains fromone to five carbon atoms, alkoxy wherein the alkyl portion thereofcontains from one to five carbon atoms, phenoxy, alkoxyalkyl wherein thealkyl portion thereof contains from one to five carbon atoms, benzyloxy,cyano, cyanoamino, alkanoyl wherein the alkyl portion thereof containsfrom one to five carbon atoms, mercapto, alkylthio wherein the alkylportion thereof contains from one to five carbon atoms, arylthio,alkylsulfinyl wherein the alkyl portion thereof contains from one tofive carbon atoms, alkylsulfonyl wherein the alkyl portion thereofcontains from one to five carbon atoms, arylsulfinyl and arylsulfonyl,##STR181## wherein each of R¹, R², R³ and R⁴ is independently selectedfrom hydrido, alkyl having from one to five carbon atoms and phenyl; ora pharmaceutically-acceptable salt thereof.
 2. Compound of claim 1wherein each of Y_(m) and Y_(n) is a spacer group independently selectedfrom one or more of alkyl having one to five carbon atoms, alkenyl,alkynyl, aryl selected from phenyl, biphenyl and naphthyl and aralkylwherein the alkyl portion contains from one to five carbon atoms, anyone of which spacer groups may be substituted at any substitutableposition with one or more groups selected from alkyl having one to fivecarbon atoms, cycloalkyl having from three to ten carbon atoms, oxo,exomethylene, halo, haloalkyl wherein the alkyl portion contains fromone to five carbon atoms, phenyl, benzyl, hydroxy, hydroxyalkyl whereinthe alkyl portion contains from one to five carbon atoms, alkoxy whereinthe alkyl portion contains from one to five carbon atoms, phenoxy,alkoxyalkyl wherein the alkyl portion contains from one to five carbonatoms, benzyloxy, cyano, alkanoyl wherein the alkyl portion containsfrom one to five carbon atoms, and amino and amido radicals of theformula ##STR182## wherein each of R¹, R², R³ and R⁴ is independentlyselected from hydrido, alkyl having one to five carbon atoms, phenyl andbenzyl; wherein each of m and n is a number independently selected fromzero to three, inclusive;wherein each X and T is one or more groupsindependently selected from hydrido, alkyl having one to five carbonatoms, cycloalkyl having from three to ten carbon atoms, cycloalkylalkylwherein the cycloalkyl portion contains from three to ten carbon atomsand the alkyl portion contains one to five carbon atoms, halo, haloalkylwherein the alkyl portion contains from one to five carbon atoms,alkenyl, cycloalkenyl, alkynyl, phenyl, benzyl, hydroxy, hydroxyalkylwherein the alkyl portion contains from one to five carbon atoms, alkoxywherein the alkyl portion contains from one to five carbon atoms,alkoxyalkyl wherein the alkyl portion contains from one to five carbonatoms, benzyloxy, cyano, cyanoamino, alkanoyl wherein the alkyl portioncontains from one to five carbon atoms, mercapto, alkylthio wherein thealkyl portion contains from one to five carbon atoms, arylthio,alkylsulfinyl wherein the alkyl portion contains from one to five carbonatoms, alkylsulfonyl wherein the alkyl portion contains from one to fivecarbon atoms, arylsulfinyl and arylsulfonyl, and amino and amidoradicals of the formula ##STR183## wherein each of R¹, R², R³ and R⁴ isindependently selected from hydrido, alkyl having one to five carbonatoms, phenyl and benzyl; or a pharmaceutically-acceptable salt thereof.3. Compound of claim 1 wherein each of Y_(m) and Y_(n) is a spacer groupindependently selected from one or more groups of the formula ##STR184##wherein each of R²⁷ and R²⁸ is independently selected from hydrido,alkyl having from one to five carbon atoms, cycloalkyl having from threeto ten carbon atoms, halo, haloalkyl wherein the alkyl portion containsfrom one to five carbon atoms, hydroxy, hydroxyalkyl wherein the alkylportion contains from one to five carbon atoms, alkoxy wherein the alkylportion contains from one to five carbon atoms, alkoxyalkyl wherein thealkyl portion contains from one to five carbon atoms, alkanoyl whereinthe alkyl portion contains from one to five carbon atoms, ##STR185##wherein each of R¹, R², R³ and R⁴ is independently selected from hydridoand alkyl having from one to five carbon atoms; wherein R²⁷ and R²⁸ maybe taken together to form oxo or exomethylene; wherein each of R²⁹ andR³⁰ is independently selected from hydrido, alkyl having from one tofive carbon atoms, haloalkyl wherein the alkyl portion contains from oneto five carbon atoms, hydroxyalkyl wherein the alkyl portion containsfrom one to five carbon atoms and alkoxyalkyl wherein the alkyl portioncontains from one to five carbon atoms; wherein each of m and n is anumber independently selected from zero to three, inclusive;wherein eachX and T is one or more groups independently selected from hydrido, alkylhaving from one to five carbon atoms, cycloalkyl wherein the alkylportion contains from one to five carbon atoms, halo, haloalkyl whereinthe alkyl portion contains from one to five carbon atoms, phenyl,benzyl, hydroxy, hydroxyalkyl wherein the alkyl portion contains fromone to five carbon atoms, alkoxy wherein the alkyl portion contains fromone to five carbon atoms, phenoxy, alkoxyalkyl wherein the alkyl portioncontains from one to five carbon atoms, benzyloxy, alkanoyl wherein thealkyl portion contains from one to five carbon atoms, ##STR186## whereineach of R¹, R², R³ and R⁴ is independently selected from hydrido andalkyl having from one to five carbon atoms; or apharmaceutically-acceptable salt thereof.
 4. Compound of claim 3selected from compounds and their pharmaceutically-acceptable salts, ofthe group consisting of6-chloro-α,2-bis(1H-tetrazol-5-yl)imidazo1,2-a!pyridine-5-methanol; α,2-bis(1H-tetrazol-5-yl)imidazo1,2-a!pyridine-5-methanol; 6-chloro-2-(1H-tetrazol-5-yl)-5-(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine; 2-(1H-tetrazol-5-yl)-5-(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine; 2-(1H-tetrazol-5-yl)-5-methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;α,2-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-6-methanol;6-chloro-2-(1H-tetrazol-5-yl)-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine; 7-bromo-6-2-methoxy-2-(1H-tetrazol-5-yl)ethyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 6-2-methoxy-2-(1H-tetrazol-5-yl)ethyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 7-bromo-6-2-(1H-tetrazol-5-yl)ethyl!-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6- 2-(1H-tetrazol-5-yl)ethyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 6-2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 5-2-methoxy-2-(1H-tetrazol-5-yl)ethyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 7-bromo-6-2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 7-bromo-6-3-methoxy-3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 6-3-methoxy-3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 7-bromo-6-3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6- 3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 6-3-hydroxy-3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 5-3-methoxy-3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 7-bromo-6-3-hydroxy-3-(1H-tetrazol-5-yl)propyl!-2-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 6-chloro-2,5-bis(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6-hydroxy-2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6-methoxy-2,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;2,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;2,7-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;5-chloro-2,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6-chloro-3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6-hydroxy-3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6-methoxy-3,5-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;3,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;3,7-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;5-chloro-3,6-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;6-chloro-α,3-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;α,3-bis(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine-5-methanol;6-chloro-3-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine; 3-(1H-tetrazol-5-yl)-5- (1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine; 3-(1H-tetrazol-5-yl)-5-methoxy(1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;3-(1H-tetrazol-5-yl)-6- (1H-tetrazol-5-yl)methyl!imidazo 1,2-a!pyridine;6-chloro-3-(1H-tetrazol-5-yl)-5- methoxy(1H-tetrazol-5-yl)methyl!imidazo1,2-a!pyridine; 6-chloro-5-2-methoxy-2-(1H-tetrazol-5-yl)ethyl!-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 5-2-methoxy-2-(1H-tetrazol-5-yl)ethyl!-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 6-chloro-5-2-(1H-tetrazol-5-yl)ethyl!-3-(1H-tetrazol-5-yl)imidazo 1,2-a!pyridine;5- 2-(1H-tetrazol-5-yl)ethyl!-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 5-2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; 6-2-methoxy-2-(1H-tetrazol-5-yl)ethyl!-3-(1H-tetrazol-5-yl)imidazo1,2-a!pyridine; and 6-chloro-5-2-hydroxy-2-(1H-tetrazol-5-yl)ethyl!tetrazol-5-yl)imidazo1,2-a!pyridine.5.
 5. A pharmaceutical composition comprising atherapeutically-effective amount of an active compound and apharmaceutically-acceptable carrier or diluent, said active compoundselected from a compound of claim
 2. 6. A pharmaceutical compositioncomprising a therapeutically-effective amount of an active compound anda pharmaceutically-acceptable carrier or diluent, said active compoundselected from a compound of claim
 1. 7. A pharmaceutical compositioncomprising a therapeutically-effective amount of an active compound anda pharmaceutically-acceptable carrier or diluent, said active compoundselected from a compound of claim
 3. 8. A pharmaceutical compositioncomprising a therapeutically-effective amount of an active compound anda pharmaceutically-acceptable carrier or diluent, said active compoundselected from a compound of claim
 4. 9. A method to treat excitatoryamino acid induced neurotoxic injury mediated by the NMDA receptor in asubject, which method comprises administering to said subject atherapeutically-effective amount of a compound of claim
 2. 10. A methodto treat excitatory amino acid induced neurotoxic injury mediated by theNMDA receptor in a subject, which method comprises administering to saidsubject a therapeutically-effective amount of a compound of claim
 1. 11.A method to treat excitatory amino acid induced neurotoxic injurymediated by the NMDA receptor in a subject, which method comprisesadministering to said subject a therapeutically-effective amount of acompound of claim
 3. 12. A method to treat excitatory amino acid inducedneurotoxic injury mediated by the NMDA receptor in a subject, whichmethod comprises administering to said subject atherapeutically-effective amount of a compound of claim
 4. 13. Themethod of claim 12 for use in treating hypoxia, anoxia or ischemia. 14.The method of claim 13 for use in treating ischemia.